chrX-37008427-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001013736.3(FAM47C):​c.17C>A​(p.Pro6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,203,306 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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: 𝑓 0.0000088 (0 hom., 1 hem., cov: 25)
  • Exomes 𝑓: 0.0000028 (0 hom. 2 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14718378).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47C	NM_001013736.3	c.17C>A	p.Pro6Gln	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>A	p.Pro6Gln	missense_variant	Exon 1 of 1	6	NM_001013736.3	ENSP00000367913.3

Frequencies

GnomAD3 genomes AF: 0.00000883 AC: 1 AN: 113298 Hom.: 0 Cov.: 25 AF XY: 0.0000282 AC XY: 1 AN XY: 35430

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000187

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 3 AN: 1090008 Hom.: 0 Cov.: 34 AF XY: 0.00000560 AC XY: 2 AN XY: 357026

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: 0.00000359

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000883 AC: 1 AN: 113298 Hom.: 0 Cov.: 25 AF XY: 0.0000282 AC XY: 1 AN XY: 35430

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000187

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.4
DANN	Benign	0.95
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.024
Sift	Benign	0.041	D
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.11
MutPred		0.11		Loss of glycosylation at S11 (P = 0.1724);
MVP		0.061
MPC		0.66
ClinPred		0.39	T
GERP RS		-0.92
Varity_R		0.17
gMVP		0.042

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;