Variant 1-70270934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_030816.5(ANKRD13C):c.1417G>A(p.Val473Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,458,802 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 1 hom. )

Consequence

ANKRD13C
NM_030816.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.04

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06856421).

BP6

Variant 1-70270934-C-T is Benign according to our data. Variant chr1-70270934-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2364064.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13C	NM_030816.5 linkuse as main transcript	c.1417G>A	p.Val473Ile	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 linkuse as main transcript	c.1417G>A	p.Val473Ile	missense_variant	12/13	1	NM_030816.5	ENSP00000359982	P1	Q8N6S4-1
ANKRD13C	ENST00000262346.6 linkuse as main transcript	c.1312G>A	p.Val438Ile	missense_variant	11/12	1		ENSP00000262346		Q8N6S4-2
ANKRD13C	ENST00000464236.1 linkuse as main transcript	n.201G>A		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250066

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458802

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.16

N;.

MutationTaster

Benign

0.70

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.27

N;N

REVEL

Benign

0.076

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.16

MutPred

0.41

Gain of catalytic residue at P475 (P = 0.0339);.;

MVP

0.12

MPC

0.51

ClinPred

0.18

GERP RS

4.9

Varity_R

0.040

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over