chrX-37008426-C-A

Variant names:

• chrX-37008426-C-A
• rs377377914
• NM_001013736.3:c.16C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013736.3(FAM47C):​c.16C>A​(p.Pro6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,468 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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. P6S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: FAM47C NM_001013736.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10351461).

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.16C>A	p.Pro6Thr	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.16C>A	p.Pro6Thr	missense	Exon 1 of 1	ENSP00000367913.3	Q5HY64

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.18e-7 AC: 1 AN: 1089468 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 356604

African (AFR) AF: 0.00 AC: 0 AN: 26200

American (AMR) AF: 0.00 AC: 0 AN: 34765

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19178

East Asian (EAS) AF: 0.00 AC: 0 AN: 29954

South Asian (SAS) AF: 0.0000187 AC: 1 AN: 53474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4038

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 835994

Other (OTH) AF: 0.00 AC: 0 AN: 45615

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.0
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.017
Sift	Uncertain	0.025	D
Sift4G	Benign	0.099	T
Polyphen		0.63	P
Vest4		0.041
MutPred		0.12		Gain of phosphorylation at P6 (P = 0.005)
MVP		0.067
MPC		0.62
ClinPred		0.84	D
GERP RS		0.46
PromoterAI		-0.020	Neutral
Varity_R		0.30
gMVP		0.049
Mutation Taster		=99/1	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: rs377377914; hg19: chrX-37026499;