rs782697581

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-37008427-C-T
• chrX-37008427-C-A
• chrX-37008427-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001013736.3(FAM47C):​c.17C>T​(p.Pro6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,203,299 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.000015 (0 hom. 8 hem.)
• Consequence: FAM47C NM_001013736.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.934
• Publications: 0 publications found

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]

FAM47C Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: XL Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06126687).
• BS2: High Hemizygotes in GnomAdExome4 at 8 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013736.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47C	NM_001013736.3	MANE Select	c.17C>T	p.Pro6Leu	missense	Exon 1 of 1	NP_001013758.1	Q5HY64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47C	ENST00000358047.5	TSL:6 MANE Select	c.17C>T	p.Pro6Leu	missense	Exon 1 of 1	ENSP00000367913.3	Q5HY64

Frequencies

GnomAD3 genomes AF: 0.0000177 AC: 2 AN: 113298 Hom.: 0 Cov.: 25

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: 0.0000375

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000581 AC: 1 AN: 172044 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000147 AC: 16 AN: 1090001 Hom.: 0 Cov.: 34 AF XY: 0.0000224 AC XY: 8 AN XY: 357025

African (AFR) AF: 0.00 AC: 0 AN: 26198

American (AMR) AF: 0.00 AC: 0 AN: 34790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19202

East Asian (EAS) AF: 0.0000334 AC: 1 AN: 29970

South Asian (SAS) AF: 0.00 AC: 0 AN: 53538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40265

Middle Eastern (MID) AF: 0.000494 AC: 2 AN: 4045

European-Non Finnish (NFE) AF: 0.0000132 AC: 11 AN: 836359

Other (OTH) AF: 0.0000438 AC: 2 AN: 45634

GnomAD4 genome AF: 0.0000177 AC: 2 AN: 113298 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35430

African (AFR) AF: 0.00 AC: 0 AN: 31230

American (AMR) AF: 0.00 AC: 0 AN: 10859

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2661

East Asian (EAS) AF: 0.00 AC: 0 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 2823

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000375 AC: 2 AN: 53394

Other (OTH) AF: 0.00 AC: 0 AN: 1536

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.90
DEOGEN2	Benign	0.0089	T
FATHMM_MKL	Benign	0.00048	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.93
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.017
Sift	Benign	0.037	D
Sift4G	Benign	0.23	T
Polyphen		0.16	B
Vest4		0.052
MutPred		0.12		Loss of glycosylation at S11 (P = 0.1859)
MVP		0.048
MPC		0.21
ClinPred		0.082	T
GERP RS		-0.92
PromoterAI		-0.028	Neutral
Varity_R		0.10
gMVP		0.034
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs782697581; hg19: chrX-37026500;