chr3-184342171-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144635.5(FAM131A):​c.431C>T​(p.Ser144Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,882 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: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FAM131A
NM_144635.5 missense

Scores

3
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40305775).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM131ANM_144635.5 linkuse as main transcriptc.431C>T p.Ser144Leu missense_variant 4/6 ENST00000383847.7 NP_653236.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM131AENST00000383847.7 linkuse as main transcriptc.431C>T p.Ser144Leu missense_variant 4/62 NM_144635.5 ENSP00000373360 A1Q6UXB0-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251434
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 GeneticsApr 01, 2024The c.431C>T (p.S144L) alteration is located in exon 4 (coding exon 4) of the FAM131A gene. This alteration results from a C to T substitution at nucleotide position 431, causing the serine (S) at amino acid position 144 to be replaced by a leucine (L). 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
0.14
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
29
DANN
Pathogenic
1.0
Eigen
Uncertain
0.67
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;D;.;D;D;D;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.40
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.0
.;.;.;.;.;.;.;.;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-3.0
D;D;D;D;D;.;D;D;D
REVEL
Benign
0.17
Sift
Uncertain
0.0080
D;D;D;D;D;.;D;D;D
Sift4G
Uncertain
0.021
D;D;D;D;D;.;D;D;D
Polyphen
0.99
.;D;.;.;.;.;.;.;.
Vest4
0.23
MutPred
0.22
.;.;.;.;.;.;.;.;Loss of phosphorylation at S113 (P = 0.026);
MVP
0.45
MPC
1.1
ClinPred
0.88
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.27
gMVP
0.44

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: rs769003578; hg19: chr3-184059959; API