rs377599440

Variant summary

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

The NM_182623.3(FAM131C):​c.404A>T​(p.His135Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,363,348 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H135R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 19)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

FAM131C
NM_182623.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0160
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=0.07444075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM131CNM_182623.3 linkc.404A>T p.His135Leu missense_variant Exon 5 of 7 ENST00000375662.5 NP_872429.2 Q96AQ9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM131CENST00000375662.5 linkc.404A>T p.His135Leu missense_variant Exon 5 of 7 1 NM_182623.3 ENSP00000364814.4 Q96AQ9
FAM131CENST00000494078.1 linkn.478A>T non_coding_transcript_exon_variant Exon 4 of 6 3

Frequencies

GnomAD3 genomes
Cov.:
19
GnomAD3 exomes
AF:
0.00000405
AC:
1
AN:
247218
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134734
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:
0.00000895
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000147
AC:
2
AN:
1363348
Hom.:
0
Cov.:
49
AF XY:
0.00
AC XY:
0
AN XY:
676998
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:
0.00000189
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
19
ExAC
AF:
0.00000826
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
3.1
DANN
Benign
0.96
DEOGEN2
Benign
0.029
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.074
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.042
Sift
Benign
0.044
D
Sift4G
Benign
0.12
T
Polyphen
0.49
P
Vest4
0.17
MutPred
0.26
Loss of disorder (P = 0.0755);
MVP
0.37
MPC
0.86
ClinPred
0.26
T
GERP RS
2.2
Varity_R
0.11
gMVP
0.35

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: rs377599440; hg19: chr1-16386411; API