Variant 10-59254419-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198215.4(FAM13C):c.1261A>G(p.Ile421Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,551,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

FAM13C
NM_198215.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

FAM13C (HGNC:19371): (family with sequence similarity 13 member C)

FAM13C links:

Genome browser will be placed here

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=0.058746576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM13C	NM_198215.4 linkuse as main transcript	c.1261A>G	p.Ile421Val	missense_variant	11/14	ENST00000618804.5	NP_937858.2	Q8NE31-1A8K181

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM13C	ENST00000618804.5 linkuse as main transcript	c.1261A>G	p.Ile421Val	missense_variant	11/14	1	NM_198215.4	ENSP00000481854.1		Q8NE31-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000921

AC:

AN:

217110

Hom.:

AF XY:

0.00000847

AC XY:

AN XY:

118074

show subpopulations

Gnomad AFR exome

AF:

0.0000721

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:

0.00

Gnomad OTH exome

AF:

0.000200

GnomAD4 exome

AF:

0.00000715

AC:

AN:

1398832

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

694518

show subpopulations

Gnomad4 AFR exome

AF:

0.000194

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000697

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 24, 2024

The c.1261A>G (p.I421V) alteration is located in exon 11 (coding exon 11) of the FAM13C gene. This alteration results from a A to G substitution at nucleotide position 1261, causing the isoleucine (I) at amino acid position 421 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

Benign

0.096

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.50

DEOGEN2

Benign

0.0063

T;.;.;.;.;.;.;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

D;T;D;T;T;D;T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.059

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.050

N;.;.;.;.;.;.;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.040

.;.;.;.;.;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

.;.;.;.;.;T;T;T

Sift4G

Benign

0.66

T;T;T;T;T;T;T;T

Polyphen

0.0060

B;.;.;.;B;.;B;B

Vest4

0.14

MutPred

0.28

Loss of catalytic residue at P423 (P = 0.0309);.;.;.;.;.;Loss of catalytic residue at P423 (P = 0.0309);Loss of catalytic residue at P423 (P = 0.0309);

MVP

0.65

ClinPred

0.040

GERP RS

4.3

Varity_R

0.053

gMVP

0.30

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