X-13042926-T-C

Position:

• chrX-13042926-T-C

Variant summary

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

The NM_174901.6(FAM9C):​c.206A>G​(p.Asp69Gly) 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. 13/20 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: FAM9C NM_174901.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.319

Genes affected

FAM9C (HGNC:18405): (family with sequence similarity 9 member C) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be localized to the nucleus as the protein contains several nuclear localization signals, and has similarity to a synaptonemal complex protein. [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=0.08960998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM9C	NM_174901.6	c.206A>G	p.Asp69Gly	missense_variant	4/8	ENST00000380625.8
FAM9C	XM_024452348.2	c.518A>G	p.Asp173Gly	missense_variant	4/7
FAM9C	XM_005274460.4	c.206A>G	p.Asp69Gly	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9C	ENST00000380625.8	c.206A>G	p.Asp69Gly	missense_variant	4/8	1	NM_174901.6	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.206A>G (p.D69G) alteration is located in exon 4 (coding exon 3) of the FAM9C gene. This alteration results from a A to G substitution at nucleotide position 206, causing the aspartic acid (D) at amino acid position 69 to be replaced by a glycine (G). 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	0.20
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.085	T;T;T
FATHMM_MKL	Benign	0.00086	N
LIST_S2	Benign	0.43	T;.;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.090	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.5	D;N;N
REVEL	Benign	0.076
Sift	Benign	0.061	T;T;T
Sift4G	Benign	0.070	T;T;T
Polyphen		0.24	.;B;B
Vest4		0.21
MutPred		0.22		Loss of stability (P = 0.0346);Loss of stability (P = 0.0346);Loss of stability (P = 0.0346);
MVP		0.84
MPC		0.013
ClinPred		0.20	T
GERP RS		-1.4
Varity_R		0.13
gMVP		0.039

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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-13061045;