1-70354156-C-T

Variant names:

• chr1-70354156-C-T
• rs1342386297
• NM_030816.5:c.253G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030816.5(ANKRD13C):​c.253G>A​(p.Val85Met) 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. 14/22 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. V85L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD13C NM_030816.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367
• Publications: 0 publications found

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]

ACMG classification

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=0.13327959).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030816.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD13C	NM_030816.5	MANE Select	c.253G>A	p.Val85Met	missense	Exon 1 of 13	NP_110443.3	Q8N6S4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD13C	ENST00000370944.9	TSL:1 MANE Select	c.253G>A	p.Val85Met	missense	Exon 1 of 13	ENSP00000359982.4	Q8N6S4-1
	ANKRD13C	ENST00000262346.6	TSL:1	c.253G>A	p.Val85Met	missense	Exon 1 of 12	ENSP00000262346.6	Q8N6S4-2
	ANKRD13C	ENST00000888140.1		c.253G>A	p.Val85Met	missense	Exon 1 of 14	ENSP00000558200.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.37
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.056
Sift	Benign	0.13	T
Sift4G	Benign	0.21	T
Polyphen		0.78	P
Vest4		0.19
MutPred		0.21		Loss of glycosylation at S84 (P = 0.046)
MVP		0.49
MPC		0.64
ClinPred		0.64	D
GERP RS		2.0
Varity_R		0.070
gMVP		0.24
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1342386297; hg19: chr1-70819839;