X-37008778-C-T

Variant names:

• chrX-37008778-C-T
• NM_001013736.3:c.368C>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.368C>T​(p.Ala123Val) 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. 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: -0.817

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=0.14764524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47C	NM_001013736.3	c.368C>T	p.Ala123Val	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.368C>T	p.Ala123Val	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

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.368C>T (p.A123V) 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 368, causing the alanine (A) at amino acid position 123 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.00080	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.059
Sift	Benign	0.038	D
Sift4G	Benign	0.079	T
Polyphen		1.0	D
Vest4		0.10
MutPred		0.19		Gain of ubiquitination at K128 (P = 0.0754);
MVP		0.14
MPC		0.29
ClinPred		0.85	D
GERP RS		0.50
Varity_R		0.082
gMVP		0.090

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-37026851;