Variant 10-59352401-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198215.4(FAM13C):c.193C>T(p.Pro65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,613,982 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00094 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

FAM13C
NM_198215.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.262

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012680978).

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM13C	NM_198215.4 linkuse as main transcript	c.193C>T	p.Pro65Ser	missense_variant	3/14	ENST00000618804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM13C	ENST00000618804.5 linkuse as main transcript	c.193C>T	p.Pro65Ser	missense_variant	3/14	1	NM_198215.4	A1	Q8NE31-1

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

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:

0.00132

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.000717

AC:

180

AN:

251072

Hom.:

AF XY:

0.000788

AC XY:

107

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00149

AC:

2179

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1034

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00184

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152278

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00119

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.000593

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.00178

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

Aug 12, 2021

The c.193C>T (p.P65S) alteration is located in exon 3 (coding exon 3) of the FAM13C gene. This alteration results from a C to T substitution at nucleotide position 193, causing the proline (P) at amino acid position 65 to be replaced by a serine (S). 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

0.075

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.58

Cadd

Benign

0.51

Dann

Benign

0.82

DEOGEN2

Benign

0.0021

T;.;.;.;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.58

T;T;T;T;T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.013

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

N;.;.;N;.;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.33

Sift4G

Benign

0.79

T;T;T;T;T;T

Polyphen

0.013

B;.;.;B;B;.

Vest4

0.19

MVP

0.52

ClinPred

0.014

GERP RS

0.95

Varity_R

0.020

gMVP

0.034

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