dbSNP rs559597076: AHDC1:p.Pro1231Leu (chr1-27548424-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001371928.1(AHDC1):c.3692C>T(p.Pro1231Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

AHDC1
NM_001371928.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25135377).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHDC1	NM_001371928.1 link	c.3692C>T	p.Pro1231Leu	missense_variant	Exon 8 of 9	ENST00000673934.1	NP_001358857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHDC1	ENST00000673934.1 link	c.3692C>T	p.Pro1231Leu	missense_variant	Exon 8 of 9		NM_001371928.1	ENSP00000501218.1		Q5TGY3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459842

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725876

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

Uncertain:1

Mar 05, 2018

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T;T;T

Eigen

Benign

-0.011

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

.;.;D;.;.

M_CAP

Benign

0.061

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.0

L;L;L;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.4

D;.;D;.;.

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;.;D;.;.

Sift4G

Uncertain

0.0050

D;.;D;.;.

Polyphen

0.043

B;B;B;B;B

Vest4

0.84

MutPred

0.26

Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);

MVP

0.35

MPC

1.4

ClinPred

0.99

GERP RS

3.6

Varity_R

0.30

gMVP

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over