Variant 17-49716184-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_030802.4(FAM117A):c.1042C>T(p.Arg348Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,440,348 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 0.000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

FAM117A
NM_030802.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

FAM117A (HGNC:24179): (family with sequence similarity 117 member A)

FAM117A links:

ENSG00000250751 (HGNC:):

ENSG00000250751 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27148595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM117A	NM_030802.4 link	c.1042C>T	p.Arg348Cys	missense_variant	7/8	ENST00000240364.7	NP_110429.1	Q9C073-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM117A	ENST00000240364.7 link	c.1042C>T	p.Arg348Cys	missense_variant	7/8	1	NM_030802.4	ENSP00000240364.2		Q9C073-1

Frequencies

GnomAD3 genomes

AF:

0.0000681

AC:

AN:

146830

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000742

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:

0.000311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000601

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

251166

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.000308

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:

0.0000924

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000881

AC:

114

AN:

1293518

Hom.:

Cov.:

AF XY:

0.0000748

AC XY:

AN XY:

642080

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

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:

0.000268

Gnomad4 NFE exome

AF:

0.0000895

Gnomad4 OTH exome

AF:

0.000163

GnomAD4 genome

AF:

0.0000681

AC:

AN:

146830

Hom.:

Cov.:

AF XY:

0.0000698

AC XY:

AN XY:

71602

show subpopulations

Gnomad4 AFR

AF:

0.0000742

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000311

Gnomad4 NFE

AF:

0.0000601

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Oct 25, 2024

The c.1042C>T (p.R348C) alteration is located in exon 7 (coding exon 7) of the FAM117A gene. This alteration results from a C to T substitution at nucleotide position 1042, causing the arginine (R) at amino acid position 348 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

T;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.8

D;.

REVEL

Benign

0.24

Sift

Uncertain

0.0010

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.55

MutPred

0.44

Gain of sheet (P = 0.0827);.;

MVP

0.19

MPC

1.6

ClinPred

0.83

GERP RS

5.5

Varity_R

0.47

gMVP

0.67

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