1-16058523-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182623.3(FAM131C):​c.757C>A​(p.Pro253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,521,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 47)
Exomes 𝑓: 0.0000088 ( 0 hom. )

Consequence

FAM131C
NM_182623.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0130
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.019438177).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM131CNM_182623.3 linkc.757C>A p.Pro253Thr missense_variant 7/7 ENST00000375662.5 NP_872429.2 Q96AQ9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM131CENST00000375662.5 linkc.757C>A p.Pro253Thr missense_variant 7/71 NM_182623.3 ENSP00000364814.4 Q96AQ9
FAM131CENST00000494078.1 linkn.831C>A non_coding_transcript_exon_variant 6/63

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152256
Hom.:
0
Cov.:
47
show subpopulations
Gnomad AFR
AF:
0.000337
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000877
AC:
12
AN:
1369010
Hom.:
0
Cov.:
82
AF XY:
0.00000891
AC XY:
6
AN XY:
673514
show subpopulations
Gnomad4 AFR exome
AF:
0.000257
Gnomad4 AMR exome
AF:
0.0000657
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:
9.37e-7
Gnomad4 OTH exome
AF:
0.0000177
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152374
Hom.:
0
Cov.:
47
AF XY:
0.0000939
AC XY:
7
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000253
Hom.:
0
ExAC
AF:
0.0000289
AC:
2

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 GeneticsNov 12, 2024The c.757C>A (p.P253T) alteration is located in exon 7 (coding exon 7) of the FAM131C gene. This alteration results from a C to A substitution at nucleotide position 757, causing the proline (P) at amino acid position 253 to be replaced by a threonine (T). 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
0.072
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
9.9
DANN
Benign
0.97
DEOGEN2
Benign
0.013
T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.019
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.027
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.40
T
Polyphen
0.63
P
Vest4
0.054
MutPred
0.12
Gain of phosphorylation at P253 (P = 0.0083);
MVP
0.32
MPC
1.2
ClinPred
0.017
T
GERP RS
2.4
Varity_R
0.048
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs569806191; hg19: chr1-16385018; API