5-138345049-C-T

Variant names:

• chr5-138345049-C-T
• NM_016605.3:c.361C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016605.3(FAM53C):​c.361C>T​(p.Leu121Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: FAM53C NM_016605.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53C	NM_016605.3	c.361C>T	p.Leu121Phe	missense_variant	Exon 4 of 5	ENST00000239906.10	NP_057689.1
FAM53C	NM_001135647.2	c.361C>T	p.Leu121Phe	missense_variant	Exon 4 of 5		NP_001129119.1
FAM53C	NM_001350195.2	c.331C>T	p.Leu111Phe	missense_variant	Exon 4 of 5		NP_001337124.1
FAM53C	NM_001350194.2	c.137-409C>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.361C>T	p.Leu121Phe	missense_variant	Exon 4 of 5	1	NM_016605.3	ENSP00000239906.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461702 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727130

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: 0.00000630

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.361C>T (p.L121F) alteration is located in exon 4 (coding exon 3) of the FAM53C gene. This alteration results from a C to T substitution at nucleotide position 361, causing the leucine (L) at amino acid position 121 to be replaced by a phenylalanine (F). 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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;T;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.10	T;T;D
Polyphen		1.0	D;D;.
Vest4		0.68
MutPred		0.48		Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);.;
MVP		0.26
MPC		0.85
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.82
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-137680738;