Genetic Variant FAM9A:p.Glu262ArgfsTer16 (chrX-8795123-TTC-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_174951.3(FAM9A):c.784_785delGA(p.Glu262ArgfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,135,791 control chromosomes in the GnomAD database, including 1 homozygotes. There are 90 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00023 ( 1 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.00028 ( 0 hom. 85 hem. )

Consequence

FAM9A
NM_174951.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.279

Variant links:

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]

FAM9A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-8795123-TTC-T is Benign according to our data. Variant chrX-8795123-TTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659948.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM9A	NM_174951.3 link	c.784_785delGA	p.Glu262ArgfsTer16	frameshift_variant	Exon 7 of 10	ENST00000381003.7	NP_777611.1	Q8IZU1
FAM9A	NM_001171186.1 link	c.784_785delGA	p.Glu262ArgfsTer16	frameshift_variant	Exon 7 of 10		NP_001164657.1	Q8IZU1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM9A	ENST00000381003.7 link	c.784_785delGA	p.Glu262ArgfsTer16	frameshift_variant	Exon 7 of 10	1	NM_174951.3	ENSP00000370391.3		Q8IZU1
FAM9A	ENST00000543214.1 link	c.784_785delGA	p.Glu262ArgfsTer16	frameshift_variant	Exon 7 of 10	1		ENSP00000440163.1		Q8IZU1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

110697

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

32917

show subpopulations

Gnomad AFR

AF:

0.000198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000193

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000785

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000278

AC:

AN:

136561

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

33417

show subpopulations

Gnomad AFR exome

AF:

0.0000884

Gnomad AMR exome

AF:

0.000212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000422

Gnomad SAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000391

Gnomad OTH exome

AF:

0.000285

GnomAD4 exome

AF:

0.000276

AC:

283

AN:

1025039

Hom.:

AF XY:

0.000282

AC XY:

AN XY:

301527

show subpopulations

Gnomad4 AFR exome

AF:

0.000202

Gnomad4 AMR exome

AF:

0.000312

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000305

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000282

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.000235

AC:

AN:

110752

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

32982

show subpopulations

Gnomad4 AFR

AF:

0.000197

Gnomad4 AMR

AF:

0.000193

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000787

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000291

Hom.:

Bravo

AF:

0.000238

Asia WGS

AF:

0.000796

AC:

AN:

2522

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM9A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over