X-37008427-C-G

Variant names:

• chrX-37008427-C-G
• rs782697581
• NM_001013736.3:c.17C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013736.3(FAM47C):​c.17C>G​(p.Pro6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000917 in 1,090,009 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
• Consequence: FAM47C NM_001013736.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054382205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47C	NM_001013736.3	c.17C>G	p.Pro6Arg	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.17C>G	p.Pro6Arg	missense_variant	Exon 1 of 1	6	NM_001013736.3	ENSP00000367913.3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.17e-7 AC: 1 AN: 1090009 Hom.: 0 Cov.: 34 AF XY: 0.00000280 AC XY: 1 AN XY: 357027

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: 0.0000187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.90
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.60	N
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.028
Sift	Benign	0.36	T
Sift4G	Benign	0.70	T
Polyphen		0.13	B
Vest4		0.056
MutPred		0.13		Gain of MoRF binding (P = 0.0103);
MVP		0.055
MPC		0.27
ClinPred		0.098	T
GERP RS		-0.92
Varity_R		0.25
gMVP		0.045

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: rs782697581; hg19: chrX-37026500;