X-13043152-A-G

Variant names:

• chrX-13043152-A-G
• NM_174901.6:c.158T>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.158T>C​(p.Phe53Ser) 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.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FAM9C NM_174901.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.556

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=0.16581994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM9C	NM_174901.6	c.158T>C	p.Phe53Ser	missense_variant	Exon 3 of 8	ENST00000380625.8	NP_777561.1
FAM9C	XM_024452348.2	c.470T>C	p.Phe157Ser	missense_variant	Exon 3 of 7		XP_024308116.2
FAM9C	XM_005274460.4	c.158T>C	p.Phe53Ser	missense_variant	Exon 3 of 8		XP_005274517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM9C	ENST00000380625.8	c.158T>C	p.Phe53Ser	missense_variant	Exon 3 of 8	1	NM_174901.6	ENSP00000369999.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158T>C (p.F53S) alteration is located in exon 3 (coding exon 2) of the FAM9C gene. This alteration results from a T to C substitution at nucleotide position 158, causing the phenylalanine (F) at amino acid position 53 to be replaced by a serine (S). 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	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T;T
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.68	T;.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-7.0	D;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D;T;T
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.91	.;P;P
Vest4		0.40
MutPred		0.15		Gain of phosphorylation at F53 (P = 0.0108);Gain of phosphorylation at F53 (P = 0.0108);Gain of phosphorylation at F53 (P = 0.0108);
MVP		0.66
MPC		0.047
ClinPred		0.88	D
GERP RS		0.41
Varity_R		0.19
gMVP		0.016

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-13061271;