rs757736241

Variant names:

• chrX-8795394-C-A
• rs757736241
• NM_174951.3:c.515G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-8795394-C-A
• chrX-8795394-C-T

Variant summary

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

The NM_174951.3(FAM9A):​c.515G>T​(p.Arg172Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,087,493 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. 13/19 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. R172Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
• Consequence: FAM9A NM_174951.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 0 publications found

Genes affected

FAM9A (HGNC:18403): (family with sequence similarity 9 member A) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be a nuclear protein that is localized to the nucleolus, and has some similarity to a synaptonemal complex protein. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Aug 2011]

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=0.11605954).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174951.3. 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
	FAM9A	NM_174951.3	MANE Select	c.515G>T	p.Arg172Leu	missense	Exon 7 of 10	NP_777611.1	Q8IZU1
	FAM9A	NM_001171186.1		c.515G>T	p.Arg172Leu	missense	Exon 7 of 10	NP_001164657.1	Q8IZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM9A	ENST00000381003.7	TSL:1 MANE Select	c.515G>T	p.Arg172Leu	missense	Exon 7 of 10	ENSP00000370391.3	Q8IZU1
	FAM9A	ENST00000543214.1	TSL:1	c.515G>T	p.Arg172Leu	missense	Exon 7 of 10	ENSP00000440163.1	Q8IZU1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000276 AC: 3 AN: 1087493 Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 1 AN XY: 355403

African (AFR) AF: 0.00 AC: 0 AN: 26136

American (AMR) AF: 0.0000287 AC: 1 AN: 34819

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19158

East Asian (EAS) AF: 0.00 AC: 0 AN: 29983

South Asian (SAS) AF: 0.00 AC: 0 AN: 53303

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40351

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2929

European-Non Finnish (NFE) AF: 0.00000239 AC: 2 AN: 835267

Other (OTH) AF: 0.00 AC: 0 AN: 45547

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.73
DANN	Benign	0.18
DEOGEN2	Benign	0.0032	T
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-0.075
PROVEAN	Benign	0.57	N
REVEL	Benign	0.087
Sift	Benign	0.47	T
Sift4G	Benign	0.33	T
Polyphen		0.88	P
Vest4		0.12
MutPred		0.30		Loss of methylation at K173 (P = 0.0516)
MVP		0.27
MPC		0.33
ClinPred		0.15	T
GERP RS		-1.2
Varity_R		0.078
gMVP		0.031
Mutation Taster		=95/5	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: rs757736241; hg19: chrX-8763435;