X-8795287-C-T

Variant names:

• chrX-8795287-C-T
• rs201732308
• NM_174951.3:c.622G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174951.3(FAM9A):​c.622G>A​(p.Glu208Lys) 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. 13/17 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. E208Q) 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: -1.26

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07621622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM9A	NM_174951.3	c.622G>A	p.Glu208Lys	missense_variant	Exon 7 of 10	ENST00000381003.7	NP_777611.1
FAM9A	NM_001171186.1	c.622G>A	p.Glu208Lys	missense_variant	Exon 7 of 10		NP_001164657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM9A	ENST00000381003.7	c.622G>A	p.Glu208Lys	missense_variant	Exon 7 of 10	1	NM_174951.3	ENSP00000370391.3
FAM9A	ENST00000543214.1	c.622G>A	p.Glu208Lys	missense_variant	Exon 7 of 10	1		ENSP00000440163.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.88
DEOGEN2	Benign	0.0042	T;T
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.32	T;.
M_CAP	Benign	0.00046	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PROVEAN	Benign	-0.35	N;N
REVEL	Benign	0.081
Sift	Benign	0.20	T;T
Sift4G	Uncertain	0.018	D;D
Polyphen		0.59	P;P
Vest4		0.15
MutPred		0.23		Gain of ubiquitination at E208 (P = 0.0054);Gain of ubiquitination at E208 (P = 0.0054);
MVP		0.26
MPC		0.059
ClinPred		0.15	T
Varity_R		0.14
gMVP		0.079

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

Publications

LitVar

Other links and lift over

dbSNP: rs201732308; hg19: chrX-8763328;