NM_001371928.1:c.4749C>G

Variant names:

• chr1-27547367-G-C
• rs747550510
• NM_001371928.1:c.4749C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371928.1(AHDC1):​c.4749C>G​(p.Ser1583Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1583S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AHDC1 NM_001371928.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.342026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHDC1	NM_001371928.1	c.4749C>G	p.Ser1583Arg	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	c.4749C>G	p.Ser1583Arg	missense_variant	Exon 8 of 9		NM_001371928.1	ENSP00000501218.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	.;.;T;.;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.34	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L;L;L;L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.6	N;.;N;.;.
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;.;D;.;.
Sift4G	Uncertain	0.018	D;.;D;.;.
Polyphen		1.0	D;D;D;D;D
Vest4		0.78
MutPred		0.19		Loss of glycosylation at S1583 (P = 0.0041);Loss of glycosylation at S1583 (P = 0.0041);Loss of glycosylation at S1583 (P = 0.0041);Loss of glycosylation at S1583 (P = 0.0041);Loss of glycosylation at S1583 (P = 0.0041);
MVP		0.62
MPC		1.3
ClinPred		0.81	D
GERP RS		2.5
Varity_R		0.15
gMVP		0.57

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: rs747550510; hg19: chr1-27873878;