X-8795413-G-C

Variant names:

• chrX-8795413-G-C
• rs779704332
• NM_174951.3:c.496C>G

Variant summary

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

The NM_174951.3(FAM9A):​c.496C>G​(p.Arg166Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R166C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: FAM9A NM_174951.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.496C>G	p.Arg166Gly	missense	Exon 7 of 10	NP_777611.1	Q8IZU1
	FAM9A	NM_001171186.1		c.496C>G	p.Arg166Gly	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.496C>G	p.Arg166Gly	missense	Exon 7 of 10	ENSP00000370391.3	Q8IZU1
	FAM9A	ENST00000543214.1	TSL:1	c.496C>G	p.Arg166Gly	missense	Exon 7 of 10	ENSP00000440163.1	Q8IZU1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.71
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.7
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.041
Sift	Uncertain	0.013	D
Sift4G	Benign	0.29	T
Polyphen		0.88	P
Vest4		0.17
MutPred		0.22		Loss of helix (P = 0.0558)
MVP		0.19
MPC		0.33
ClinPred		0.65	D
GERP RS		0.61
Varity_R		0.30
gMVP		0.12
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs779704332; hg19: chrX-8763454;