3-184344581-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144635.5(FAM131A):​c.712G>A​(p.Val238Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,610,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

FAM131A
NM_144635.5 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98
Variant links:
Genes affected
FAM131A (HGNC:28308): (family with sequence similarity 131 member A)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16026768).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM131ANM_144635.5 linkuse as main transcriptc.712G>A p.Val238Met missense_variant 6/6 ENST00000383847.7 NP_653236.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM131AENST00000383847.7 linkuse as main transcriptc.712G>A p.Val238Met missense_variant 6/62 NM_144635.5 ENSP00000373360 A1Q6UXB0-3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248408
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134500
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000754
AC:
11
AN:
1458412
Hom.:
0
Cov.:
32
AF XY:
0.00000827
AC XY:
6
AN XY:
725138
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000757
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152206
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsJan 23, 2024The c.712G>A (p.V238M) alteration is located in exon 6 (coding exon 6) of the FAM131A gene. This alteration results from a G to A substitution at nucleotide position 712, causing the valine (V) at amino acid position 238 to be replaced by a methionine (M). 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
0.10
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Pathogenic
27
DANN
Uncertain
1.0
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.94
.;D;.;D;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.16
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
.;.;.;.;.;.;.;L
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
0.28
N;N;N;N;.;N;N;N
REVEL
Benign
0.086
Sift
Benign
0.47
T;D;T;D;.;T;T;T
Sift4G
Benign
0.23
T;T;T;T;.;T;T;T
Polyphen
1.0
.;D;.;.;.;.;.;.
Vest4
0.24
MutPred
0.13
.;.;.;.;.;.;.;Loss of glycosylation at S206 (P = 0.0564);
MVP
0.33
MPC
1.2
ClinPred
0.67
D
GERP RS
4.4
Varity_R
0.035
gMVP
0.16

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: rs776295404; hg19: chr3-184062369; API