rs9332458

Variant names:

• chr3-143331660-T-C
• rs9332458
• NM_173653.4:c.1604+31824A>G

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+31824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,020 control chromosomes in the GnomAD database, including 9,508 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 0.34 (9508 hom., cov: 32)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1604+31824A>G		intron_variant	Intron 14 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1711+31717A>G		intron_variant	Intron 14 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.1253+31824A>G		intron_variant	Intron 13 of 14		XP_016861692.1
SLC9A9	XM_011512703.4	c.956+31824A>G		intron_variant	Intron 11 of 12		XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1604+31824A>G		intron_variant	Intron 14 of 15	1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51241 AN: 151902 Hom.: 9503 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.337 AC: 51281 AN: 152020 Hom.: 9508 Cov.: 32 AF XY: 0.340 AC XY: 25292 AN XY: 74310

African (AFR) AF: 0.491 AC: 20311 AN: 41398

American (AMR) AF: 0.373 AC: 5695 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 949 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1218 AN: 5172

South Asian (SAS) AF: 0.186 AC: 898 AN: 4818

European-Finnish (FIN) AF: 0.377 AC: 3986 AN: 10580

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17357 AN: 67982

Other (OTH) AF: 0.308 AC: 648 AN: 2106

Alfa AF: 0.283 Hom.: 17870

Bravo AF: 0.347

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.37
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9332458; hg19: chr3-143050502;