5-138345178-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11143139).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016605.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53C	NM_016605.3	MANE Select	c.490C>T	p.Pro164Ser	missense	Exon 4 of 5	NP_057689.1	Q9NYF3
	FAM53C	NM_001135647.2		c.490C>T	p.Pro164Ser	missense	Exon 4 of 5	NP_001129119.1	Q9NYF3
	FAM53C	NM_001350195.2		c.460C>T	p.Pro154Ser	missense	Exon 4 of 5	NP_001337124.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53C	ENST00000239906.10	TSL:1 MANE Select	c.490C>T	p.Pro164Ser	missense	Exon 4 of 5	ENSP00000239906.5	Q9NYF3
	FAM53C	ENST00000434981.6	TSL:1	c.490C>T	p.Pro164Ser	missense	Exon 4 of 5	ENSP00000403705.2	Q9NYF3
	FAM53C	ENST00000513056.5	TSL:1	c.137-218C>T		intron	N/A	ENSP00000425154.1	D6RE00

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.0081
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.16
Sift	Benign	0.24	T
Sift4G	Benign	0.22	T
Polyphen		0.11	B
Vest4		0.55
MutPred		0.21		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
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs386352301; hg19: chr5-137680867;