X-154506862-G-A

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

2

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]

Genome browser will be placed here

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
FAM3ANM_021806.4 linkc.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
FAM3AENST00000447601.7 linkc.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:
31
AN:
112942
Hom.:
0
Cov.:
24
AF XY:
0.000200
AC XY:
7
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.:
0
AF XY:
0.000791
AC XY:
53
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.:
1
Cov.:
30
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:
31
AN:
112992
Hom.:
0
Cov.:
24
AF XY:
0.000199
AC XY:
7
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.:
6
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
Oct 10, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

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.

Other links and lift over

dbSNP: rs200836674; hg19: chrX-153735193; API