rs729511

Variant names:

• chr3-143336865-G-A
• rs729511
• NM_173653.4:c.1604+26619C>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+26619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,876 control chromosomes in the GnomAD database, including 23,196 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 0.53 (23196 hom., cov: 31)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 6 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 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+26619C>T		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+26619C>T		intron	N/A	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80888 AN: 151758 Hom.: 23164 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.533 AC: 80978 AN: 151876 Hom.: 23196 Cov.: 31 AF XY: 0.530 AC XY: 39341 AN XY: 74234

African (AFR) AF: 0.743 AC: 30777 AN: 41430

American (AMR) AF: 0.538 AC: 8196 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1601 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1213 AN: 5172

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4814

European-Finnish (FIN) AF: 0.518 AC: 5458 AN: 10532

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30676 AN: 67908

Other (OTH) AF: 0.522 AC: 1100 AN: 2108

Alfa AF: 0.516 Hom.: 3523

Bravo AF: 0.547

Asia WGS AF: 0.322 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.41
DANN	Benign	0.68
PhyloP100		-2.1
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: rs729511; hg19: chr3-143055707;