rs7628692

Variant names:

• chr3-143363170-T-G
• rs7628692
• NM_173653.4:c.1604+314A>C

Variant summary

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

The NM_173653.4(SLC9A9):​c.1604+314A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,000 control chromosomes in the GnomAD database, including 10,224 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 0.36 (10224 hom., cov: 32)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173653.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	NM_173653.4	MANE Select	c.1604+314A>C		intron	N/A	NP_775924.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	ENST00000316549.11	TSL:1 MANE Select	c.1604+314A>C		intron	N/A	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55116 AN: 151882 Hom.: 10214 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.363 AC: 55157 AN: 152000 Hom.: 10224 Cov.: 32 AF XY: 0.371 AC XY: 27570 AN XY: 74292

African (AFR) AF: 0.370 AC: 15312 AN: 41418

American (AMR) AF: 0.403 AC: 6158 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1088 AN: 3472

East Asian (EAS) AF: 0.354 AC: 1826 AN: 5156

South Asian (SAS) AF: 0.321 AC: 1546 AN: 4822

European-Finnish (FIN) AF: 0.496 AC: 5244 AN: 10566

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22914 AN: 67976

Other (OTH) AF: 0.360 AC: 759 AN: 2108

Alfa AF: 0.340 Hom.: 27130

Bravo AF: 0.359

Asia WGS AF: 0.380 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		0.0
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: rs7628692; hg19: chr3-143082012;