rs199608514

Variant names:

• chrX-8795299-C-T
• rs199608514
• NM_174951.3:c.610G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-8795299-C-T
• chrX-8795299-C-A
• chrX-8795299-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_174951.3(FAM9A):​c.610G>A​(p.Ala204Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,198,906 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.00013 (0 hom. 38 hem.)
• Consequence: FAM9A NM_174951.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.071309626).
• BS2: High Hemizygotes in GnomAdExome4 at 38 gene

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.610G>A	p.Ala204Thr	missense	Exon 7 of 10	NP_777611.1	Q8IZU1
	FAM9A	NM_001171186.1		c.610G>A	p.Ala204Thr	missense	Exon 7 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.610G>A	p.Ala204Thr	missense	Exon 7 of 10	ENSP00000370391.3	Q8IZU1
	FAM9A	ENST00000543214.1	TSL:1	c.610G>A	p.Ala204Thr	missense	Exon 7 of 10	ENSP00000440163.1	Q8IZU1

Frequencies

GnomAD3 genomes AF: 0.0000727 AC: 8 AN: 109989 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00426

Gnomad NFE AF: 0.000114

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000118 AC: 20 AN: 168968 AF XY: 0.0000848

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: 0.000244

Gnomad OTH exome AF: 0.000472

GnomAD4 exome AF: 0.000130 AC: 142 AN: 1088863 Hom.: 0 Cov.: 31 AF XY: 0.000106 AC XY: 38 AN XY: 357075

African (AFR) AF: 0.00 AC: 0 AN: 26217

American (AMR) AF: 0.00 AC: 0 AN: 34634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19332

East Asian (EAS) AF: 0.00 AC: 0 AN: 29894

South Asian (SAS) AF: 0.0000373 AC: 2 AN: 53585

European-Finnish (FIN) AF: 0.0000261 AC: 1 AN: 38242

Middle Eastern (MID) AF: 0.00197 AC: 6 AN: 3049

European-Non Finnish (NFE) AF: 0.000154 AC: 129 AN: 838316

Other (OTH) AF: 0.0000877 AC: 4 AN: 45594

GnomAD4 genome AF: 0.0000727 AC: 8 AN: 110043 Hom.: 0 Cov.: 22 AF XY: 0.0000309 AC XY: 1 AN XY: 32405

African (AFR) AF: 0.0000331 AC: 1 AN: 30220

American (AMR) AF: 0.00 AC: 0 AN: 10163

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2629

East Asian (EAS) AF: 0.00 AC: 0 AN: 3499

South Asian (SAS) AF: 0.00 AC: 0 AN: 2532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5856

Middle Eastern (MID) AF: 0.00467 AC: 1 AN: 214

European-Non Finnish (NFE) AF: 0.000114 AC: 6 AN: 52770

Other (OTH) AF: 0.00 AC: 0 AN: 1485

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.000113

ExAC AF: 0.0000839 AC: 10

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	0.27
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.1
DANN	Benign	0.89
DEOGEN2	Benign	0.0081	T
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.00063	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.21
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.044
Sift	Benign	0.22	T
Sift4G	Uncertain	0.012	D
Polyphen		0.85	P
Vest4		0.16
MVP		0.50
MPC		0.052
ClinPred		0.026	T
GERP RS		0.15
Varity_R		0.089
gMVP		0.021
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs199608514; hg19: chrX-8763340; COSMIC: COSV66813093;