rs1135401946

Positions:

• chr1-27551779-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001371928.1(AHDC1):​c.337A>T​(p.Asn113Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. N113N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHDC1 NM_001371928.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-27551779-T-A is Benign according to our data. Variant chr1-27551779-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 431372.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHDC1	NM_001371928.1	c.337A>T	p.Asn113Tyr	missense_variant	8/9	ENST00000673934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHDC1	ENST00000673934.1	c.337A>T	p.Asn113Tyr	missense_variant	8/9		NM_001371928.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues

Apr 26, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T;T;T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.56	.;.;T;.;.
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.55	N;N;N;N;N
MutationTaster	Benign	0.95	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N;.;N;.;.
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;.;D;.;.
Sift4G	Benign	0.64	T;.;T;.;.
Polyphen		1.0	D;D;D;D;D
Vest4		0.76
MutPred		0.57		Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);
MVP		0.20
MPC		1.6
ClinPred		0.84	D
GERP RS		4.0
Varity_R		0.29
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

Other links and lift over

dbSNP: rs1135401946; hg19: chr1-27878290;