Genetic Variant ANKRD13C:p.Ile399Val (chr1-70292408-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030816.5(ANKRD13C):c.1195A>G(p.Ile399Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000504 in 1,586,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

ANKRD13C
NM_030816.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

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=0.04371804).

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.1195A>G	p.Ile399Val	missense	Exon 9 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.1195A>G	p.Ile399Val	missense	Exon 9 of 13	ENSP00000359982.4	Q8N6S4-1
ANKRD13C	ENST00000262346.6	TSL:1	c.1090A>G	p.Ile364Val	missense	Exon 8 of 12	ENSP00000262346.6	Q8N6S4-2
ANKRD13C	ENST00000888140.1		c.1324A>G	p.Ile442Val	missense	Exon 10 of 14	ENSP00000558200.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000879

AC:

AN:

227648

AF XY:

0.00000808

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:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000488

AC:

AN:

1434224

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

713120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24950

East Asian (EAS)

AF:

0.00

AC:

AN:

39162

South Asian (SAS)

AF:

0.00

AC:

AN:

80194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.00000634

AC:

AN:

1104738

Other (OTH)

AF:

0.00

AC:

AN:

59296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.071

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.012

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0037

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

PhyloP100

1.6

PrimateAI

Benign

0.48

PROVEAN

Benign

0.14

REVEL

Benign

0.031

Sift

Benign

0.22

Sift4G

Benign

0.53

Polyphen

0.0010

Vest4

0.087

MutPred

0.13

Gain of MoRF binding (P = 0.2232)

MVP

0.25

MPC

0.52

ClinPred

0.034

GERP RS

0.055

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.20

Mutation Taster

=96/4

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