rs147276945

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.1411G>A(p.Val471Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00845 in 1,608,408 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 80 hom. )

Consequence

AHDC1
NM_001371928.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.44

Publications

7 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=0.00791198).

BP6

Variant 1-27550705-C-T is Benign according to our data. Variant chr1-27550705-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376920.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 = 0.00612 (933/152392) while in subpopulation NFE AF = 0.0104 (706/68044). AF 95% confidence interval is 0.00974. There are 2 homozygotes in GnomAd4. There are 439 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 933 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.1411G>A	p.Val471Met	missense	Exon 8 of 9	NP_001358857.1	Q5TGY3
	AHDC1	NM_001029882.3		c.1411G>A	p.Val471Met	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.1411G>A	p.Val471Met	missense	Exon 8 of 9	ENSP00000501218.1	Q5TGY3
AHDC1	ENST00000247087.10	TSL:5	c.1411G>A	p.Val471Met	missense	Exon 5 of 6	ENSP00000247087.4	Q5TGY3
AHDC1	ENST00000374011.6	TSL:5	c.1411G>A	p.Val471Met	missense	Exon 6 of 7	ENSP00000363123.2	Q5TGY3

Frequencies

GnomAD3 genomes

AF:

0.00613

AC:

933

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00580

AC:

1374

AN:

236774

AF XY:

0.00582

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.0000576

Gnomad FIN exome

AF:

0.00294

Gnomad NFE exome

AF:

0.00966

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00870

AC:

12665

AN:

1456016

Hom.:

Cov.:

AF XY:

0.00846

AC XY:

6128

AN XY:

724006

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

33354

American (AMR)

AF:

0.00166

AC:

AN:

43964

Ashkenazi Jewish (ASJ)

AF:

0.0195

AC:

507

AN:

26004

East Asian (EAS)

AF:

0.000559

AC:

AN:

39372

South Asian (SAS)

AF:

0.000257

AC:

AN:

85470

European-Finnish (FIN)

AF:

0.00335

AC:

175

AN:

52236

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0103

AC:

11430

AN:

1109682

Other (OTH)

AF:

0.00642

AC:

386

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

923

1846

2770

3693

4616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.00612

AC:

933

AN:

152392

Hom.:

Cov.:

AF XY:

0.00589

AC XY:

439

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41600

American (AMR)

AF:

0.00202

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00216

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0104

AC:

706

AN:

68044

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

111

167

222

278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00797

Hom.:

Bravo

AF:

0.00572

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.00544

AC:

660

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

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

0.21

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

PhyloP100

1.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.47

REVEL

Benign

0.12

Sift

Uncertain

0.0020

Sift4G

Benign

0.12

Polyphen

1.0

Vest4

0.44

MVP

0.20

MPC

1.4

ClinPred

0.0098

GERP RS

4.4

Varity_R

0.11

gMVP

0.75

Mutation Taster

=94/6

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

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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