X-8793672-C-T

Variant names:

• chrX-8793672-C-T
• NM_174951.3:c.916G>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.916G>A​(p.Glu306Lys) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 0.664

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=0.24748519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM9A	NM_174951.3	c.916G>A	p.Glu306Lys	missense_variant	Exon 8 of 10	ENST00000381003.7	NP_777611.1
FAM9A	NM_001171186.1	c.916G>A	p.Glu306Lys	missense_variant	Exon 8 of 10		NP_001164657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM9A	ENST00000381003.7	c.916G>A	p.Glu306Lys	missense_variant	Exon 8 of 10	1	NM_174951.3	ENSP00000370391.3
FAM9A	ENST00000543214.1	c.916G>A	p.Glu306Lys	missense_variant	Exon 8 of 10	1		ENSP00000440163.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 09, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.916G>A (p.E306K) alteration is located in exon 8 (coding exon 7) of the FAM9A gene. This alteration results from a G to A substitution at nucleotide position 916, causing the glutamic acid (E) at amino acid position 306 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.082	T;T
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.60	T;.
M_CAP	Benign	0.00076	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.10
Sift	Benign	0.035	D;D
Sift4G	Benign	0.064	T;T
Polyphen		0.99	D;D
Vest4		0.17
MutPred		0.37		Gain of MoRF binding (P = 0.0055);Gain of MoRF binding (P = 0.0055);
MVP		0.23
MPC		0.059
ClinPred		0.21	T
GERP RS		0.68
Varity_R		0.13
gMVP		0.088

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-8761713;