NM_174951.3:c.259C>T

Variant names:

• chrX-8798441-G-A
• rs1260714082
• NM_174951.3:c.259C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174951.3(FAM9A):​c.259C>T​(p.Pro87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,097,775 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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 (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: FAM9A NM_174951.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.583
• 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: 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=0.15064475).

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.259C>T	p.Pro87Ser	missense	Exon 4 of 10	NP_777611.1	Q8IZU1
	FAM9A	NM_001171186.1		c.259C>T	p.Pro87Ser	missense	Exon 4 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.259C>T	p.Pro87Ser	missense	Exon 4 of 10	ENSP00000370391.3	Q8IZU1
	FAM9A	ENST00000543214.1	TSL:1	c.259C>T	p.Pro87Ser	missense	Exon 4 of 10	ENSP00000440163.1	Q8IZU1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00 AC: 0 AN: 182482 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1097775 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363147

African (AFR) AF: 0.00 AC: 0 AN: 26387

American (AMR) AF: 0.00 AC: 0 AN: 35147

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19365

East Asian (EAS) AF: 0.00 AC: 0 AN: 30184

South Asian (SAS) AF: 0.00 AC: 0 AN: 53942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 842013

Other (OTH) AF: 0.00 AC: 0 AN: 46081

GnomAD4 genome Cov.: 24

EpiCase AF: 0.0000547

EpiControl AF: 0.00

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	0.17
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.7
DANN	Benign	0.93
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.00053	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.58
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.028
Sift	Benign	0.076	T
Sift4G	Benign	0.38	T
Polyphen		1.0	D
Vest4		0.077
MutPred		0.22		Gain of phosphorylation at P87 (P = 0.0071)
MVP		0.11
MPC		0.33
ClinPred		0.37	T
GERP RS		0.74
Varity_R		0.092
gMVP		0.18
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

dbSNP: rs1260714082; hg19: chrX-8766482; COSMIC: COSV105318383;