rs2166775

Variant names:

• chr3-143785691-G-A
• rs2166775
• NM_173653.4:c.533+9310C>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.533+9310C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,792 control chromosomes in the GnomAD database, including 25,753 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 0.55 (25753 hom., cov: 30)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 2 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 = 0.804 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	NM_173653.4	MANE Select	c.533+9310C>T		intron	N/A	NP_775924.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	ENST00000316549.11	TSL:1 MANE Select	c.533+9310C>T		intron	N/A	ENSP00000320246.6
	SLC9A9	ENST00000900956.1		c.533+9310C>T		intron	N/A	ENSP00000571015.1
	SLC9A9	ENST00000474727.2	TSL:4	n.*144+9310C>T		intron	N/A	ENSP00000419090.2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 83972 AN: 151674 Hom.: 25713 Cov.: 30

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.554 AC: 84070 AN: 151792 Hom.: 25753 Cov.: 30 AF XY: 0.560 AC XY: 41528 AN XY: 74160

African (AFR) AF: 0.811 AC: 33582 AN: 41392

American (AMR) AF: 0.518 AC: 7904 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1807 AN: 3464

East Asian (EAS) AF: 0.754 AC: 3895 AN: 5168

South Asian (SAS) AF: 0.680 AC: 3266 AN: 4802

European-Finnish (FIN) AF: 0.425 AC: 4457 AN: 10486

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27462 AN: 67900

Other (OTH) AF: 0.547 AC: 1155 AN: 2110

Alfa AF: 0.454 Hom.: 26008

Bravo AF: 0.569

Asia WGS AF: 0.706 AC: 2451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		0.0
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: rs2166775; hg19: chr3-143504533;