X-37008666-C-T

Variant names:

• chrX-37008666-C-T
• NM_001013736.3:c.256C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013736.3(FAM47C):​c.256C>T​(p.Pro86Ser) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: FAM47C NM_001013736.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.184

Genes affected

FAM47C (HGNC:25301): (family with sequence similarity 47 member C) This gene encodes a product belonging to a family of proteins with unknown function. The coding sequence of this family member includes several tandemly repeated regions. [provided by RefSeq, Sep 2011]

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=0.10068941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47C	NM_001013736.3	c.256C>T	p.Pro86Ser	missense_variant	Exon 1 of 1	ENST00000358047.5	NP_001013758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47C	ENST00000358047.5	c.256C>T	p.Pro86Ser	missense_variant	Exon 1 of 1	6	NM_001013736.3	ENSP00000367913.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.256C>T (p.P86S) alteration is located in exon 1 (coding exon 1) of the FAM47C gene. This alteration results from a C to T substitution at nucleotide position 256, causing the proline (P) at amino acid position 86 to be replaced by a serine (S). 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	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.00040	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.031
Sift	Benign	0.049	D
Sift4G	Benign	0.13	T
Polyphen		0.22	B
Vest4		0.055
MutPred		0.31		Gain of phosphorylation at P86 (P = 0.0035);
MVP		0.072
MPC		0.26
ClinPred		0.91	D
GERP RS		-0.69
Varity_R		0.078
gMVP		0.060

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: chrX-37026739;