Genetic Variant FAM3A:p.Pro214Pro (chrX-154506862-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_021806.4(FAM3A):c.642C>T(p.Pro214Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000371 in 1,210,623 control chromosomes in the GnomAD database, including 1 homozygotes. There are 183 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 7 hem., cov: 24)

Exomes 𝑓: 0.00038 ( 1 hom. 176 hem. )

Consequence

FAM3A
NM_021806.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.17

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant X-154506862-G-A is Benign according to our data. Variant chrX-154506862-G-A is described in ClinVar as [Benign]. Clinvar id is 736968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.17 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3A	NM_021806.4 link	c.642C>T	p.Pro214Pro	synonymous_variant	Exon 9 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.642C>T	p.Pro214Pro	synonymous_variant	Exon 9 of 9	1	NM_021806.4	ENSP00000416146.2		P98173-1

Frequencies

GnomAD3 genomes

AF:

0.000274

AC:

AN:

112942

Hom.:

Cov.:

AF XY:

0.000200

AC XY:

AN XY:

35080

show subpopulations

Gnomad AFR

AF:

0.000192

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000933

Gnomad ASJ

AF:

0.00150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000300

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000566

AC:

103

AN:

182072

Hom.:

AF XY:

0.000791

AC XY:

AN XY:

66986

show subpopulations

Gnomad AFR exome

AF:

0.000229

Gnomad AMR exome

AF:

0.000767

Gnomad ASJ exome

AF:

0.000805

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00211

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000358

Gnomad OTH exome

AF:

0.000888

GnomAD4 exome

AF:

0.000381

AC:

418

AN:

1097631

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

176

AN XY:

363029

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.000654

Gnomad4 ASJ exome

AF:

0.00150

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00272

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.000521

GnomAD4 genome

AF:

0.000274

AC:

AN:

112992

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

35140

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.0000932

Gnomad4 ASJ

AF:

0.00150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00107

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000300

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.000287

EpiCase

AF:

0.000654

EpiControl

AF:

0.000831

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

- -

Oct 10, 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

-0.75

CADD

Benign

1.2

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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