3-184338396-A-T

Variant summary

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

The NM_144635.5(FAM131A):​c.98A>T​(p.Asp33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000594 in 1,447,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

FAM131A
NM_144635.5 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52
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=0.19861662).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM131ANM_144635.5 linkuse as main transcriptc.98A>T p.Asp33Val missense_variant 2/6 ENST00000383847.7 NP_653236.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM131AENST00000383847.7 linkuse as main transcriptc.98A>T p.Asp33Val missense_variant 2/62 NM_144635.5 ENSP00000373360 A1Q6UXB0-3

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
151940
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000273
AC:
2
AN:
73266
Hom.:
0
AF XY:
0.0000532
AC XY:
2
AN XY:
37574
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:
0.0000636
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000594
AC:
77
AN:
1295434
Hom.:
0
Cov.:
30
AF XY:
0.0000650
AC XY:
41
AN XY:
630464
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000715
Gnomad4 OTH exome
AF:
0.0000557
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
151940
Hom.:
0
Cov.:
33
AF XY:
0.0000539
AC XY:
4
AN XY:
74228
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000378
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
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 GeneticsJun 03, 2022The c.98A>T (p.D33V) alteration is located in exon 2 (coding exon 2) of the FAM131A gene. This alteration results from a A to T substitution at nucleotide position 98, causing the aspartic acid (D) at amino acid position 33 to be replaced by a valine (V). 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
0.31
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
22
DANN
Benign
0.95
Eigen
Benign
0.044
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.2
.;N
REVEL
Benign
0.11
Sift
Benign
0.14
.;T
Sift4G
Uncertain
0.0060
.;D
Vest4
0.63
MutPred
0.34
Gain of MoRF binding (P = 0.0245);Gain of MoRF binding (P = 0.0245);
MVP
0.28
MPC
0.58
ClinPred
0.21
T
GERP RS
4.3
Varity_R
0.12
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs748509797; hg19: chr3-184056184; API