1-16059926-C-T

Variant summary

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

The NM_182623.3(FAM131C):​c.394G>A​(p.Glu132Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,539,720 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 0.00054 ( 0 hom., cov: 25)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

FAM131C
NM_182623.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45
Variant links:
Genes affected
FAM131C (HGNC:26717): (family with sequence similarity 131 member C)

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=0.097810745).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM131CNM_182623.3 linkc.394G>A p.Glu132Lys missense_variant 5/7 ENST00000375662.5 NP_872429.2 Q96AQ9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM131CENST00000375662.5 linkc.394G>A p.Glu132Lys missense_variant 5/71 NM_182623.3 ENSP00000364814.4 Q96AQ9
FAM131CENST00000494078.1 linkn.468G>A non_coding_transcript_exon_variant 4/63

Frequencies

GnomAD3 genomes
AF:
0.000537
AC:
44
AN:
81992
Hom.:
0
Cov.:
25
show subpopulations
Gnomad AFR
AF:
0.00121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000448
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:
0.00
Gnomad OTH
AF:
0.00279
GnomAD3 exomes
AF:
0.0000571
AC:
14
AN:
245250
Hom.:
0
AF XY:
0.0000821
AC XY:
11
AN XY:
133940
show subpopulations
Gnomad AFR exome
AF:
0.000671
Gnomad AMR exome
AF:
0.0000582
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:
0.00000904
Gnomad OTH exome
AF:
0.000168
GnomAD4 exome
AF:
0.0000316
AC:
46
AN:
1457638
Hom.:
0
Cov.:
52
AF XY:
0.0000303
AC XY:
22
AN XY:
725120
show subpopulations
Gnomad4 AFR exome
AF:
0.00120
Gnomad4 AMR exome
AF:
0.0000672
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
AF:
0.000536
AC:
44
AN:
82082
Hom.:
0
Cov.:
25
AF XY:
0.000579
AC XY:
23
AN XY:
39716
show subpopulations
Gnomad4 AFR
AF:
0.00120
Gnomad4 AMR
AF:
0.000448
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00276
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.000283
ESP6500AA
AF:
0.000236
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000579
AC:
7

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 GeneticsOct 20, 2024The c.394G>A (p.E132K) alteration is located in exon 5 (coding exon 5) of the FAM131C gene. This alteration results from a G to A substitution at nucleotide position 394, causing the glutamic acid (E) at amino acid position 132 to be replaced by a lysine (K). 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
0.11
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.062
T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.058
Sift
Uncertain
0.0090
D
Sift4G
Uncertain
0.060
T
Polyphen
0.95
P
Vest4
0.42
MVP
0.43
MPC
1.2
ClinPred
0.082
T
GERP RS
4.7
Varity_R
0.17
gMVP
0.33

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: rs374943695; hg19: chr1-16386421; API