5-138345178-C-T

Variant names:

• chr5-138345178-C-T
• rs386352301
• NM_016605.3:c.490C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.75

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]

ACMG classification

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
FAM53C	NM_016605.3	c.490C>T	p.Pro164Ser	missense_variant	Exon 4 of 5	ENST00000239906.10	NP_057689.1
FAM53C	NM_001135647.2	c.490C>T	p.Pro164Ser	missense_variant	Exon 4 of 5		NP_001129119.1
FAM53C	NM_001350195.2	c.460C>T	p.Pro154Ser	missense_variant	Exon 4 of 5		NP_001337124.1
FAM53C	NM_001350194.2	c.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
FAM53C	ENST00000239906.10	c.490C>T	p.Pro164Ser	missense_variant	Exon 4 of 5	1	NM_016605.3	ENSP00000239906.5

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

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

Other links and lift over

dbSNP: rs386352301; hg19: chr5-137680867;