Variant 4-2663247-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366318.2(FAM193A):c.2038A>G(p.Ser680Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,612,630 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 64 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 74 hom. )

Consequence

FAM193A
NM_001366318.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.231

Variant links:

Genes affected

FAM193A (HGNC:16822): (family with sequence similarity 193 member A)

FAM193A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019822419).

BP6

Variant 4-2663247-A-G is Benign according to our data. Variant chr4-2663247-A-G is described in ClinVar as [Benign]. Clinvar id is 773677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM193A	NM_001366318.2 linkuse as main transcript	c.2038A>G	p.Ser680Gly	missense_variant	12/21	ENST00000637812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM193A	ENST00000637812.2 linkuse as main transcript	c.2038A>G	p.Ser680Gly	missense_variant	12/21	5	NM_001366318.2	A2

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2675

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00814

AC:

2024

AN:

248632

Hom.:

AF XY:

0.00721

AC XY:

971

AN XY:

134720

show subpopulations

Gnomad AFR exome

AF:

0.0514

Gnomad AMR exome

AF:

0.00605

Gnomad ASJ exome

AF:

0.000302

Gnomad EAS exome

AF:

0.0181

Gnomad SAS exome

AF:

0.00710

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00336

Gnomad OTH exome

AF:

0.00563

GnomAD4 exome

AF:

0.00523

AC:

7639

AN:

1460336

Hom.:

Cov.:

AF XY:

0.00515

AC XY:

3745

AN XY:

726480

show subpopulations

Gnomad4 AFR exome

AF:

0.0542

Gnomad4 AMR exome

AF:

0.00683

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.0145

Gnomad4 SAS exome

AF:

0.00713

Gnomad4 FIN exome

AF:

0.00187

Gnomad4 NFE exome

AF:

0.00338

Gnomad4 OTH exome

AF:

0.00736

GnomAD4 genome

AF:

0.0176

AC:

2681

AN:

152294

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1328

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0514

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0170

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00306

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00997

Hom.:

Bravo

AF:

0.0202

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.0472

AC:

208

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00940

AC:

1141

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00344

EpiControl

AF:

0.00368

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.0

DANN

Benign

0.94

DEOGEN2

Benign

0.0036

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

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.67

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

MetaRNN

Benign

0.0020

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

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

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.58

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

REVEL

Benign

0.011

Sift

Benign

0.27

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

Sift4G

Benign

0.070

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

Polyphen

0.034, 0.082

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

Vest4

0.20, 0.21, 0.22, 0.28

MVP

0.15

MPC

0.16

ClinPred

0.0067

GERP RS

1.7

Varity_R

0.032

gMVP

0.14

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