chr3-143337625-G-A

Variant names:

• chr3-143337625-G-A
• rs7632299
• NM_173653.4:c.1604+25859C>T

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+25859C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,996 control chromosomes in the GnomAD database, including 5,412 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 0.26 (5412 hom., cov: 32)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 11 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1604+25859C>T		intron_variant	Intron 14 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1711+25752C>T		intron_variant	Intron 14 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.1253+25859C>T		intron_variant	Intron 13 of 14		XP_016861692.1
SLC9A9	XM_011512703.4	c.956+25859C>T		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+25859C>T		intron_variant	Intron 14 of 15	1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39535 AN: 151878 Hom.: 5409 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.260 AC: 39558 AN: 151996 Hom.: 5412 Cov.: 32 AF XY: 0.264 AC XY: 19602 AN XY: 74294

African (AFR) AF: 0.324 AC: 13443 AN: 41450

American (AMR) AF: 0.333 AC: 5073 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1202 AN: 5160

South Asian (SAS) AF: 0.144 AC: 693 AN: 4816

European-Finnish (FIN) AF: 0.305 AC: 3220 AN: 10548

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14440 AN: 67980

Other (OTH) AF: 0.248 AC: 523 AN: 2110

Alfa AF: 0.223 Hom.: 14648

Bravo AF: 0.267

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.93
PhyloP100		-0.30
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: rs7632299; hg19: chr3-143056467;