3-143686821-G-A

Variant names:

• chr3-143686821-G-A
• rs2360867
• NM_173653.4:c.649+6371C>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.649+6371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,958 control chromosomes in the GnomAD database, including 14,317 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 0.43 (14317 hom., cov: 31)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.649+6371C>T		intron_variant	Intron 5 of 15	ENST00000316549.11	NP_775924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.649+6371C>T		intron_variant	Intron 5 of 15	1	NM_173653.4	ENSP00000320246.6
SLC9A9	ENST00000483124.1	n.186+6371C>T		intron_variant	Intron 2 of 5	4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65456 AN: 151840 Hom.: 14303 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.431 AC: 65499 AN: 151958 Hom.: 14317 Cov.: 31 AF XY: 0.434 AC XY: 32218 AN XY: 74274

African (AFR) AF: 0.389 AC: 16117 AN: 41456

American (AMR) AF: 0.502 AC: 7655 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2478 AN: 5166

South Asian (SAS) AF: 0.604 AC: 2904 AN: 4810

European-Finnish (FIN) AF: 0.384 AC: 4053 AN: 10554

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29364 AN: 67922

Other (OTH) AF: 0.450 AC: 951 AN: 2114

Alfa AF: 0.436 Hom.: 61106

Bravo AF: 0.430

Asia WGS AF: 0.531 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.54
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: rs2360867; hg19: chr3-143405663;