rs729511

Positions:

• chr3-143336865-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A9	NM_173653.4	c.1604+26619C>T		intron_variant		ENST00000316549.11
SLC9A9	XM_011512703.4	c.956+26619C>T		intron_variant
SLC9A9	XM_017006202.3	c.1711+26512C>T		intron_variant
SLC9A9	XM_017006203.2	c.1253+26619C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1604+26619C>T		intron_variant		1	NM_173653.4	P1

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

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.522

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.41
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs729511; hg19: chr3-143055707;