rs143346525

Positions:

chr1-27550606-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 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

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 Benign. Variant got -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 [Likely_benign]. Clinvar id is 377281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-27550606-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 266 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHDC1	NM_001371928.1 linkuse as main transcript	c.1510G>A	p.Val504Met	missense_variant	8/9	ENST00000673934.1	NP_001358857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHDC1	ENST00000673934.1 linkuse as main transcript	c.1510G>A	p.Val504Met	missense_variant	8/9		NM_001371928.1	ENSP00000501218	P1

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

GnomAD3 exomes

AF:

0.00171

AC:

428

AN:

250522

Hom.:

AF XY:

0.00178

AC XY:

241

AN XY:

135614

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 SAS exome

AF:

0.000457

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

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.000340

Gnomad4 NFE exome

AF:

0.00380

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00175

AC:

266

AN:

152410

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74538

show subpopulations

Gnomad4 AFR

AF:

0.000937

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00303

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00264

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

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	AHDC1: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 16, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

AHDC1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 06, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;T;T;T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.84

.;.;T;.;.

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0066

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;N;N;N;N

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.23

N;.;N;.;.

REVEL

Benign

0.096

Sift

Uncertain

0.0070

D;.;D;.;.

Sift4G

Benign

0.19

T;.;T;.;.

Polyphen

0.97

D;D;D;D;D

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

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