1-27551904-G-A

Position:

chr1-27551904-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001371928.1(AHDC1):c.212C>T(p.Thr71Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00586 in 1,593,968 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0060 ( 31 hom. )

Consequence

AHDC1
NM_001371928.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.65

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=0.006389588).

BP6

Variant 1-27551904-G-A is Benign according to our data. Variant chr1-27551904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377378.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 = 0.00411 (623/151440) while in subpopulation NFE AF= 0.00673 (456/67738). AF 95% confidence interval is 0.00622. There are 3 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 623 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHDC1	NM_001371928.1 linkuse as main transcript	c.212C>T	p.Thr71Ile	missense_variant	8/9	ENST00000673934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHDC1	ENST00000673934.1 linkuse as main transcript	c.212C>T	p.Thr71Ile	missense_variant	8/9		NM_001371928.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

621

AN:

151326

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00302

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.00407

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00673

Gnomad OTH

AF:

0.00338

GnomAD3 exomes

AF:

0.00383

AC:

873

AN:

228156

Hom.:

AF XY:

0.00375

AC XY:

469

AN XY:

125142

show subpopulations

Gnomad AFR exome

AF:

0.00115

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.00474

Gnomad NFE exome

AF:

0.00661

Gnomad OTH exome

AF:

0.00519

GnomAD4 exome

AF:

0.00605

AC:

8721

AN:

1442528

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

4195

AN XY:

715244

show subpopulations

Gnomad4 AFR exome

AF:

0.000787

Gnomad4 AMR exome

AF:

0.00140

Gnomad4 ASJ exome

AF:

0.000158

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000956

Gnomad4 FIN exome

AF:

0.00461

Gnomad4 NFE exome

AF:

0.00735

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00411

AC:

623

AN:

151440

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

284

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.00150

Gnomad4 AMR

AF:

0.00315

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00147

Gnomad4 FIN

AF:

0.00407

Gnomad4 NFE

AF:

0.00673

Gnomad4 OTH

AF:

0.00334

Alfa

AF:

0.00449

Hom.:

Bravo

AF:

0.00398

ESP6500AA

AF:

0.000956

AC:

ESP6500EA

AF:

0.00509

AC:

ExAC

AF:

0.00382

AC:

457

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 03, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 19, 2016	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	AHDC1: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 30, 2019

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;T;T;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.54

.;.;T;.;.

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.0064

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.2

N;.;N;.;.

REVEL

Benign

0.10

Sift

Uncertain

0.011

D;.;D;.;.

Sift4G

Uncertain

0.049

D;.;D;.;.

Polyphen

0.0090

B;B;B;B;B

Vest4

0.15

MVP

0.082

MPC

1.3

ClinPred

0.015

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.096

gMVP

0.16

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