5-138345178-C-T

Variant summary

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

The NM_016605.3(FAM53C):​c.490C>T​(p.Pro164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P164A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

FAM53C
NM_016605.3 missense

Scores

3
16

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.75
Variant links:
Genes affected
FAM53C (HGNC:1336): (family with sequence similarity 53 member C) The protein encoded by this gene belongs to the FAM53 protein family. FAM53 protein family members bind to a transcriptional regulator that modulates cell proliferation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

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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=0.11143139).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM53CNM_016605.3 linkc.490C>T p.Pro164Ser missense_variant Exon 4 of 5 ENST00000239906.10 NP_057689.1 Q9NYF3
FAM53CNM_001135647.2 linkc.490C>T p.Pro164Ser missense_variant Exon 4 of 5 NP_001129119.1 Q9NYF3
FAM53CNM_001350195.2 linkc.460C>T p.Pro154Ser missense_variant Exon 4 of 5 NP_001337124.1
FAM53CNM_001350194.2 linkc.137-280C>T intron_variant Intron 3 of 4 NP_001337123.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM53CENST00000239906.10 linkc.490C>T p.Pro164Ser missense_variant Exon 4 of 5 1 NM_016605.3 ENSP00000239906.5 Q9NYF3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
-
Richard Lifton Laboratory, Yale University School of Medicine
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.022
T;T;T
Eigen
Benign
-0.0081
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.71
.;T;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
0.17
N;N;N
REVEL
Benign
0.16
Sift
Benign
0.24
T;T;T
Sift4G
Benign
0.22
T;T;T
Polyphen
0.11
B;B;.
Vest4
0.55
MutPred
0.21
Loss of catalytic residue at P163 (P = 0.0175);Loss of catalytic residue at P163 (P = 0.0175);.;
MVP
0.42
MPC
0.81
ClinPred
0.23
T
GERP RS
6.1
Varity_R
0.032
gMVP
0.30

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: rs386352301; hg19: chr5-137680867; API