rs143346525

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001371928.1(AHDC1):c.1510G>A(p.Val504Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,613,808 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V504V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 10 hom. )

Consequence

AHDC1
NM_001371928.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.748

Publications

10 publications found

Variant links:

Genes affected

AHDC1 (HGNC:25230): (AT-hook DNA binding motif containing 1) This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]

AHDC1 Gene-Disease associations (from GenCC):

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

AHDC1 links:

ENSG00000300470 (HGNC:):

ENSG00000300470 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065502524).

BP6

Variant 1-27550606-C-T is Benign according to our data. Variant chr1-27550606-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 377281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00175 (266/152410) while in subpopulation NFE AF = 0.00303 (206/68048). AF 95% confidence interval is 0.00269. There are 1 homozygotes in GnomAd4. There are 101 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 266 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371928.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHDC1	NM_001371928.1	MANE Select	c.1510G>A	p.Val504Met	missense	Exon 8 of 9	NP_001358857.1	Q5TGY3
	AHDC1	NM_001029882.3		c.1510G>A	p.Val504Met	missense	Exon 6 of 7	NP_001025053.1	Q5TGY3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AHDC1	ENST00000673934.1	MANE Select	c.1510G>A	p.Val504Met	missense	Exon 8 of 9	ENSP00000501218.1	Q5TGY3
AHDC1	ENST00000247087.10	TSL:5	c.1510G>A	p.Val504Met	missense	Exon 5 of 6	ENSP00000247087.4	Q5TGY3
AHDC1	ENST00000374011.6	TSL:5	c.1510G>A	p.Val504Met	missense	Exon 6 of 7	ENSP00000363123.2	Q5TGY3

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

266

AN:

152292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000940

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00171

AC:

428

AN:

250522

AF XY:

0.00178

show subpopulations

Gnomad AFR exome

AF:

0.000619

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000602

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

AF:

0.00309

AC:

4515

AN:

1461398

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

2189

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

33480

American (AMR)

AF:

0.000872

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000327

AC:

AN:

39700

South Asian (SAS)

AF:

0.000278

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000340

AC:

AN:

52952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00380

AC:

4230

AN:

1112002

Other (OTH)

AF:

0.00286

AC:

173

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

338

676

1014

1352

1690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00175

AC:

266

AN:

152410

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74538

show subpopulations

African (AFR)

AF:

0.000937

AC:

AN:

41606

American (AMR)

AF:

0.000915

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.000827

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00303

AC:

206

AN:

68048

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00256

Hom.:

Bravo

AF:

0.00181

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00179

AC:

217

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00294

EpiControl

AF:

0.00367

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

AHDC1-related disorder (1)

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Benign

0.16

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.84

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

PhyloP100

0.75

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.23

REVEL

Benign

0.096

Sift

Uncertain

0.0070

Sift4G

Benign

0.19

Polyphen

0.97

Vest4

0.36

MVP

0.39

MPC

1.4

ClinPred

0.016

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.55

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over