3-184342086-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144635.5(FAM131A):​c.346G>A​(p.Asp116Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

FAM131A
NM_144635.5 missense

Scores

8
5
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM131ANM_144635.5 linkuse as main transcriptc.346G>A p.Asp116Asn 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.346G>A p.Asp116Asn missense_variant 4/62 NM_144635.5 ENSP00000373360 A1Q6UXB0-3

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000220
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251478
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135910
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000130
AC:
190
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.000125
AC XY:
91
AN XY:
727248
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:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000162
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000220
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000226
Hom.:
0
Bravo
AF:
0.000106
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
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 GeneticsApr 24, 2024The c.346G>A (p.D116N) alteration is located in exon 4 (coding exon 4) of the FAM131A gene. This alteration results from a G to A substitution at nucleotide position 346, causing the aspartic acid (D) at amino acid position 116 to be replaced by an asparagine (N). 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
Pathogenic
0.84
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
32
DANN
Pathogenic
1.0
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
.;.;D;D;D;D;D;D
M_CAP
Benign
0.069
D
MetaRNN
Uncertain
0.60
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.57
T
MutationAssessor
Uncertain
2.4
.;.;.;.;.;.;.;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-4.6
D;D;D;D;.;D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D;D;D;D;.;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;.;D;D;D
Vest4
0.63
MVP
0.76
MPC
1.2
ClinPred
0.88
D
GERP RS
5.3
Varity_R
0.74
gMVP
0.80

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: rs558006786; hg19: chr3-184059874; API