chr1-27550881-C-T

Variant names:

Variant summary

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

The NM_001371928.1(AHDC1):c.1235G>A(p.Arg412His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00589 in 1,581,454 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R412C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0050 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 25 hom. )

Consequence

AHDC1
NM_001371928.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.374

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=0.0048695207).

BP6

Variant 1-27550881-C-T is Benign according to our data. Variant chr1-27550881-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 235372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-27550881-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00505 (769/152308) while in subpopulation AMR AF= 0.0104 (159/15312). AF 95% confidence interval is 0.00907. There are 1 homozygotes in gnomad4. There are 362 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 769 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHDC1	NM_001371928.1 link	c.1235G>A	p.Arg412His	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.1235G>A	p.Arg412His	missense_variant	Exon 8 of 9		NM_001371928.1	ENSP00000501218.1		Q5TGY3

Frequencies

GnomAD3 genomes

AF:

0.00505

AC:

769

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00694

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00553

AC:

1052

AN:

190110

Hom.:

AF XY:

0.00560

AC XY:

593

AN XY:

105926

show subpopulations

Gnomad AFR exome

AF:

0.000946

Gnomad AMR exome

AF:

0.00645

Gnomad ASJ exome

AF:

0.00929

Gnomad EAS exome

AF:

0.0000654

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.00709

Gnomad OTH exome

AF:

0.00803

GnomAD4 exome

AF:

0.00598

AC:

8547

AN:

1429146

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

4297

AN XY:

709704

show subpopulations

Gnomad4 AFR exome

AF:

0.000760

Gnomad4 AMR exome

AF:

0.00658

Gnomad4 ASJ exome

AF:

0.00766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00384

Gnomad4 FIN exome

AF:

0.00391

Gnomad4 NFE exome

AF:

0.00656

Gnomad4 OTH exome

AF:

0.00502

GnomAD4 genome

AF:

0.00505

AC:

769

AN:

152308

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

362

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00694

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00643

Hom.:

Bravo

AF:

0.00499

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000245

AC:

ESP6500EA

AF:

0.00543

AC:

ExAC

AF:

0.00473

AC:

558

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Dec 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AHDC1: BS1, BS2 -

Dec 23, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;T;T;T

Eigen

Benign

0.087

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.70

.;.;T;.;.

MetaRNN

Benign

0.0049

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.070

N;.;N;.;.

REVEL

Benign

0.10

Sift

Pathogenic

0.0

D;.;D;.;.

Sift4G

Benign

0.16

T;.;T;.;.

Polyphen

0.95

P;P;P;P;P

Vest4

0.36

MVP

0.11

MPC

1.4

ClinPred

0.018

GERP RS

3.9

Varity_R

0.21

gMVP

0.19

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