rs2800

Variant names:

• chr3-143705980-C-T
• rs2800
• NM_173653.4:c.534-12673G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173653.4(SLC9A9):​c.534-12673G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,086 control chromosomes in the GnomAD database, including 33,577 homozygotes. 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: 𝑓 0.66 (33577 hom., cov: 33)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 13 publications found

Genes affected

SLC9A9 (HGNC:20653): (solute carrier family 9 member A9) This gene encodes a sodium/proton exchanger that is a member of the solute carrier 9 protein family. The encoded protein localizes the to the late recycling endosomes and may play an important role in maintaining cation homeostasis. Mutations in this gene are associated with autism susceptibility 16 and attention-deficit/hyperactivity disorder. [provided by RefSeq, Mar 2012]

SLC9A9 Gene-Disease associations (from GenCC):

• autism, susceptibility to, 16

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.534-12673G>A		intron_variant	Intron 4 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.534-12673G>A		intron_variant	Intron 4 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.183-12673G>A		intron_variant	Intron 3 of 14		XP_016861692.1
SLC9A9	XM_011512704.4	c.534-12673G>A		intron_variant	Intron 4 of 9		XP_011511006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.534-12673G>A		intron_variant	Intron 4 of 15	1	NM_173653.4	ENSP00000320246.6
SLC9A9	ENST00000474727.2	n.*145-12673G>A		intron_variant	Intron 3 of 3	4		ENSP00000419090.2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100484 AN: 151968 Hom.: 33550 Cov.: 33

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.660

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.661 AC: 100565 AN: 152086 Hom.: 33577 Cov.: 33 AF XY: 0.656 AC XY: 48749 AN XY: 74360

African (AFR) AF: 0.693 AC: 28748 AN: 41460

American (AMR) AF: 0.642 AC: 9816 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2207 AN: 3468

East Asian (EAS) AF: 0.407 AC: 2099 AN: 5162

South Asian (SAS) AF: 0.590 AC: 2847 AN: 4826

European-Finnish (FIN) AF: 0.684 AC: 7241 AN: 10580

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45609 AN: 67994

Other (OTH) AF: 0.658 AC: 1390 AN: 2114

Alfa AF: 0.661 Hom.: 131128

Bravo AF: 0.661

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs2800; hg19: chr3-143424822;