1-27551830-G-C

Variant names:

• chr1-27551830-G-C
• NM_001371928.1:c.286C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371928.1(AHDC1):​c.286C>G​(p.Arg96Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R96C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AHDC1 NM_001371928.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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
• BP4: Computational evidence support a benign effect (MetaRNN=0.1078476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHDC1	NM_001371928.1	c.286C>G	p.Arg96Gly	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.286C>G	p.Arg96Gly	missense_variant	Exon 8 of 9		NM_001371928.1	ENSP00000501218.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459762 Hom.: 0 Cov.: 49 AF XY: 0.00000138 AC XY: 1 AN XY: 726268

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T;T;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.59	.;.;T;.;.
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.19	N;.;N;.;.
REVEL	Benign	0.15
Sift	Uncertain	0.025	D;.;D;.;.
Sift4G	Benign	0.17	T;.;T;.;.
Polyphen		0.0010	B;B;B;B;B
Vest4		0.24
MutPred		0.31		Gain of glycosylation at S93 (P = 0.0391);Gain of glycosylation at S93 (P = 0.0391);Gain of glycosylation at S93 (P = 0.0391);Gain of glycosylation at S93 (P = 0.0391);Gain of glycosylation at S93 (P = 0.0391);
MVP		0.31
MPC		1.2
ClinPred		0.50	T
GERP RS		4.0
Varity_R		0.11
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-27878341;