X-37008418-A-C

Variant names:

• chrX-37008418-A-C
• rs1200641141
• NM_001013736.3:c.8A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001013736.3(FAM47C):​c.8A>C​(p.Asp3Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000646 in 1,084,398 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 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. D3V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000065 (0 hom. 2 hem.)
• Consequence: FAM47C NM_001013736.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.124438226).
• BS2: High Hemizygotes in GnomAdExome4 at 2 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.8A>C	p.Asp3Ala	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.8A>C	p.Asp3Ala	missense	Exon 1 of 1	ENSP00000367913.3	Q5HY64

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000425 AC: 7 AN: 164542 AF XY: 0.0000385

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000271

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000646 AC: 7 AN: 1084398 Hom.: 0 Cov.: 33 AF XY: 0.00000567 AC XY: 2 AN XY: 352956

African (AFR) AF: 0.00 AC: 0 AN: 26026

American (AMR) AF: 0.000204 AC: 7 AN: 34277

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19011

East Asian (EAS) AF: 0.00 AC: 0 AN: 29838

South Asian (SAS) AF: 0.00 AC: 0 AN: 52966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3987

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 832890

Other (OTH) AF: 0.00 AC: 0 AN: 45329

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.021	T
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.56
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.037
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.016	D
Polyphen		0.81	P
Vest4		0.24
MutPred		0.21		Gain of MoRF binding (P = 0.0915)
MVP		0.048
MPC		0.78
ClinPred		0.36	T
GERP RS		-0.92
PromoterAI		0.034	Neutral
Varity_R		0.25
gMVP		0.082
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: rs1200641141; hg19: chrX-37026491;