Genetic Variant FAM3A:p.Ile118Ile (chrX-154507842-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_021806.4(FAM3A):c.354C>T(p.Ile118Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00062 in 1,193,318 control chromosomes in the GnomAD database, including 2 homozygotes. There are 192 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.00066 ( 2 hom. 188 hem. )

Consequence

FAM3A
NM_021806.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.693

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant X-154507842-G-A is Benign according to our data. Variant chrX-154507842-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661850.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.693 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3A	NM_021806.4 link	c.354C>T	p.Ile118Ile	synonymous_variant	Exon 6 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.354C>T	p.Ile118Ile	synonymous_variant	Exon 6 of 9	1	NM_021806.4	ENSP00000416146.2		P98173-1

Frequencies

GnomAD3 genomes

AF:

0.000213

AC:

AN:

112728

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34864

show subpopulations

Gnomad AFR

AF:

0.0000322

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:

0.000160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000376

Gnomad OTH

AF:

0.00131

GnomAD3 exomes

AF:

0.000261

AC:

AN:

145796

Hom.:

AF XY:

0.000268

AC XY:

AN XY:

44858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000128

Gnomad FIN exome

AF:

0.000851

Gnomad NFE exome

AF:

0.000392

Gnomad OTH exome

AF:

0.000268

GnomAD4 exome

AF:

0.000663

AC:

716

AN:

1080537

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

188

AN XY:

352051

show subpopulations

Gnomad4 AFR exome

AF:

0.0000382

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000155

Gnomad4 FIN exome

AF:

0.000836

Gnomad4 NFE exome

AF:

0.000774

Gnomad4 OTH exome

AF:

0.000661

GnomAD4 genome

AF:

0.000213

AC:

AN:

112781

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34927

show subpopulations

Gnomad4 AFR

AF:

0.0000321

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000160

Gnomad4 NFE

AF:

0.000376

Gnomad4 OTH

AF:

0.00130

Alfa

AF:

0.000434

Hom.:

Bravo

AF:

0.000257

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM3A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

3.9

DANN

Benign

0.86

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