Genetic Variant FAM3A:p.Asn131Asn (chrX-154507483-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_021806.4(FAM3A):c.393C>T(p.Asn131Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,208,016 control chromosomes in the GnomAD database, including 5 homozygotes. There are 1,564 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., 93 hem., cov: 23)

Exomes 𝑓: 0.0040 ( 4 hom. 1471 hem. )

Consequence

FAM3A
NM_021806.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.516

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant X-154507483-G-A is Benign according to our data. Variant chrX-154507483-G-A is described in ClinVar as [Benign]. Clinvar id is 770831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-154507483-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.516 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 93 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3A	NM_021806.4 link	c.393C>T	p.Asn131Asn	synonymous_variant	Exon 7 of 9	ENST00000447601.7	NP_068578.2	P98173-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3A	ENST00000447601.7 link	c.393C>T	p.Asn131Asn	synonymous_variant	Exon 7 of 9	1	NM_021806.4	ENSP00000416146.2		P98173-1

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

330

AN:

111924

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

AN XY:

34086

show subpopulations

Gnomad AFR

AF:

0.000812

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00123

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00370

Gnomad FIN

AF:

0.00114

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.00287

AC:

507

AN:

176785

Hom.:

AF XY:

0.00308

AC XY:

196

AN XY:

63581

show subpopulations

Gnomad AFR exome

AF:

0.000631

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.000410

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.00344

Gnomad NFE exome

AF:

0.00446

Gnomad OTH exome

AF:

0.00340

GnomAD4 exome

AF:

0.00396

AC:

4345

AN:

1096043

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

1471

AN XY:

361887

show subpopulations

Gnomad4 AFR exome

AF:

0.000379

Gnomad4 AMR exome

AF:

0.000967

Gnomad4 ASJ exome

AF:

0.000568

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00285

Gnomad4 FIN exome

AF:

0.00254

Gnomad4 NFE exome

AF:

0.00462

Gnomad4 OTH exome

AF:

0.00317

GnomAD4 genome

AF:

0.00295

AC:

330

AN:

111973

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

AN XY:

34145

show subpopulations

Gnomad4 AFR

AF:

0.000810

Gnomad4 AMR

AF:

0.00123

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00371

Gnomad4 FIN

AF:

0.00114

Gnomad4 NFE

AF:

0.00512

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00218

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.9

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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