NM_174901.6:c.158T>C

Variant names:

• chrX-13043152-A-G
• NM_174901.6:c.158T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 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: -0.556
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16581994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174901.6. 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
	FAM9C	NM_174901.6	MANE Select	c.158T>C	p.Phe53Ser	missense	Exon 3 of 8	NP_777561.1	Q8IZT9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM9C	ENST00000380625.8	TSL:1 MANE Select	c.158T>C	p.Phe53Ser	missense	Exon 3 of 8	ENSP00000369999.3	Q8IZT9
	FAM9C	ENST00000333995.7	TSL:1	c.158T>C	p.Phe53Ser	missense	Exon 3 of 7	ENSP00000334430.3	Q8IZT9
	FAM9C	ENST00000542843.5	TSL:1	c.158T>C	p.Phe53Ser	missense	Exon 3 of 6	ENSP00000439185.1	G3V1I3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

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	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.56
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.91	P
Vest4		0.40
MutPred		0.15		Gain of phosphorylation at F53 (P = 0.0108)
MVP		0.66
MPC		0.047
ClinPred		0.88	D
GERP RS		0.41
PromoterAI		-0.029	Neutral
Varity_R		0.19
gMVP		0.016
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chrX-13061271;