1-70270889-T-C

Position:

• chr1-70270889-T-C

Variant summary

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

The NM_030816.5(ANKRD13C):​c.1462A>G​(p.Met488Val) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD13C NM_030816.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.93

Genes affected

ANKRD13C (HGNC:25374): (ankyrin repeat domain 13C) Enables signaling receptor binding activity. Involved in protein retention in ER lumen; regulation of anoikis; and regulation of signaling receptor activity. Located in perinuclear region of cytoplasm. Colocalizes with endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD13C (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13C	NM_030816.5	c.1462A>G	p.Met488Val	missense_variant	12/13	ENST00000370944.9	NP_110443.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD13C	ENST00000370944.9	c.1462A>G	p.Met488Val	missense_variant	12/13	1	NM_030816.5	ENSP00000359982.4
ANKRD13C	ENST00000262346.6	c.1357A>G	p.Met453Val	missense_variant	11/12	1		ENSP00000262346.6
ANKRD13C	ENST00000464236.1	n.246A>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.1462A>G (p.M488V) alteration is located in exon 12 (coding exon 12) of the ANKRD13C gene. This alteration results from a A to G substitution at nucleotide position 1462, causing the methionine (M) at amino acid position 488 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.027	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.056	B;B
Vest4		0.66
MutPred		0.26		Gain of methylation at K489 (P = 0.0183);.;
MVP		0.84
MPC		0.65
ClinPred		0.88	D
GERP RS		6.0
Varity_R		0.42
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.24		Position offset: -33

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1678849901; hg19: chr1-70736572;