NM_174951.3:c.938A>G

Variant names:

• chrX-8791372-T-C
• NM_174951.3:c.938A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174951.3(FAM9A):​c.938A>G​(p.Lys313Arg) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K313E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FAM9A NM_174951.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.847
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057385445).

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.938A>G	p.Lys313Arg	missense	Exon 9 of 10	NP_777611.1	Q8IZU1
	FAM9A	NM_001171186.1		c.938A>G	p.Lys313Arg	missense	Exon 9 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.938A>G	p.Lys313Arg	missense	Exon 9 of 10	ENSP00000370391.3	Q8IZU1
	FAM9A	ENST00000543214.1	TSL:1	c.938A>G	p.Lys313Arg	missense	Exon 9 of 10	ENSP00000440163.1	Q8IZU1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.85
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.10
Sift	Benign	0.39	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.074
MutPred		0.17		Loss of ubiquitination at K313 (P = 0.0224)
MVP		0.12
MPC		0.047
ClinPred		0.082	T
GERP RS		-0.73
Varity_R		0.085
gMVP		0.0054
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chrX-8759413;