Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371928.1(AHDC1):c.1235G>T(p.Arg412Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

AHDC1
NM_001371928.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.374

Publications

0 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: Labcorp Genetics (formerly Invitae), Illumina, Orphanet, G2P, ClinGen

AHDC1 links:

ENSG00000300470 (HGNC:):

ENSG00000300470 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12938389).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHDC1	NM_001371928.1	MANE Select	c.1235G>T	p.Arg412Leu	missense	Exon 8 of 9	NP_001358857.1
	AHDC1	NM_001029882.3		c.1235G>T	p.Arg412Leu	missense	Exon 6 of 7	NP_001025053.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AHDC1	ENST00000673934.1	MANE Select	c.1235G>T	p.Arg412Leu	missense	Exon 8 of 9	ENSP00000501218.1
AHDC1	ENST00000247087.10	TSL:5	c.1235G>T	p.Arg412Leu	missense	Exon 5 of 6	ENSP00000247087.4
AHDC1	ENST00000374011.6	TSL:5	c.1235G>T	p.Arg412Leu	missense	Exon 6 of 7	ENSP00000363123.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1429146

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709704

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32912

American (AMR)

AF:

0.00

AC:

AN:

41794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25056

East Asian (EAS)

AF:

0.00

AC:

AN:

38514

South Asian (SAS)

AF:

0.00

AC:

AN:

82804

European-Finnish (FIN)

AF:

0.0000237

AC:

AN:

42164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100992

Other (OTH)

AF:

0.00

AC:

AN:

59196

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.0045

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.72

M_CAP

Benign

0.039

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PhyloP100

0.37

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.2

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Benign

0.24

Polyphen

0.28

Vest4

0.51

MutPred

0.35

Loss of methylation at R412 (P = 0.021)

MVP

0.13

MPC

1.2

ClinPred

0.37

GERP RS

3.9

Varity_R

0.30

gMVP

0.26

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs181285619

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over