Variant chr10-59251623-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198215.4(FAM13C):c.1586G>A(p.Arg529Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000154 in 1,613,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

FAM13C
NM_198215.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18866086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM13C	NM_198215.4 linkuse as main transcript	c.1586G>A	p.Arg529Gln	missense_variant	13/14	ENST00000618804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM13C	ENST00000618804.5 linkuse as main transcript	c.1586G>A	p.Arg529Gln	missense_variant	13/14	1	NM_198215.4	A1	Q8NE31-1

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000199

AC:

AN:

250854

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000300

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000157

AC:

230

AN:

1461234

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000118

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000186

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000214

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000416

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

Apr 23, 2024

The c.1586G>A (p.R529Q) alteration is located in exon 13 (coding exon 13) of the FAM13C gene. This alteration results from a G to A substitution at nucleotide position 1586, causing the arginine (R) at amino acid position 529 to be replaced by a glutamine (Q). 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

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

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

1.0

D;D;D;D;D;D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.19

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

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.7

M;.;.;.;.;.;.

MutationTaster

Benign

0.95

D;D;D;D;D;D;N

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.6

.;.;.;.;.;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0020

.;.;.;.;.;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;D;.;D

Vest4

0.63

MVP

0.81

ClinPred

0.21

GERP RS

5.7

Varity_R

0.59

gMVP

0.45

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