dbSNP rs1363458002: ANKRD13C:p.Val473Ile (chr1-70270934-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 14/22 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2364064.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1417G>A	p.Val473Ile	missense	Exon 12 of 13	NP_110443.3	Q8N6S4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD13C	ENST00000370944.9	TSL:1 MANE Select	c.1417G>A	p.Val473Ile	missense	Exon 12 of 13	ENSP00000359982.4	Q8N6S4-1
ANKRD13C	ENST00000262346.6	TSL:1	c.1312G>A	p.Val438Ile	missense	Exon 11 of 12	ENSP00000262346.6	Q8N6S4-2
ANKRD13C	ENST00000888140.1		c.1546G>A	p.Val516Ile	missense	Exon 13 of 14	ENSP00000558200.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250066

AF XY:

0.00000739

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 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

African (AFR)

AF:

0.00

AC:

AN:

33372

American (AMR)

AF:

0.0000672

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

85996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109746

Other (OTH)

AF:

0.00

AC:

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.022

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.70

M_CAP

Benign

0.0036

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.16

PhyloP100

5.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.27

REVEL

Benign

0.076

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

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

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over