Variant X-154508586-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021806.4(FAM3A):c.163A>G(p.Arg55Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000084 in 1,190,231 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )

Consequence

FAM3A
NM_021806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

FAM3A (HGNC:13749): (FAM3 metabolism regulating signaling molecule A) This gene encodes a cytokine-like protein. The expression of this gene may be regulated by peroxisome proliferator-activated receptor gamma, and the encoded protein may be involved in the regulation of glucose and lipid metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

FAM3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16408116).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM3A	NM_021806.4 linkuse as main transcript	c.163A>G	p.Arg55Gly	missense_variant	4/9	ENST00000447601.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM3A	ENST00000447601.7 linkuse as main transcript	c.163A>G	p.Arg55Gly	missense_variant	4/9	1	NM_021806.4	P1	P98173-1

Frequencies

GnomAD3 genomes

AF:

0.0000530

AC:

AN:

113138

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

35276

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000465

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:

0.000654

GnomAD4 exome

AF:

0.00000371

AC:

AN:

1077093

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

349807

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000883

GnomAD4 genome

AF:

0.0000530

AC:

AN:

113138

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

35276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000465

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:

0.000654

Bravo

AF:

0.0000756

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

Dec 09, 2023

The c.163A>G (p.R55G) alteration is located in exon 4 (coding exon 4) of the FAM3A gene. This alteration results from a A to G substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a glycine (G). 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

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.069

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

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.022

MetaRNN

Benign

0.16

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

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

MutationTaster

Benign

0.97

D;D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.7

N;.;.;N;N;N;N;N;D

REVEL

Benign

0.12

Sift

Benign

0.38

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

Sift4G

Benign

0.37

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

Polyphen

0.23

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

Vest4

0.41

MutPred

0.34

Gain of ubiquitination at K58 (P = 0.0396);Gain of ubiquitination at K58 (P = 0.0396);.;Gain of ubiquitination at K58 (P = 0.0396);Gain of ubiquitination at K58 (P = 0.0396);Gain of ubiquitination at K58 (P = 0.0396);.;Gain of ubiquitination at K58 (P = 0.0396);.;

MVP

0.20

MPC

0.54

ClinPred

0.61

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.68

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