rs16853564

Variant names:

• chr3-143410080-T-C
• rs16853564
• NM_173653.4:c.1470-27966A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173653.4(SLC9A9):​c.1470-27966A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 152,300 control chromosomes in the GnomAD database, including 250 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 0.049 (250 hom., cov: 32)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1470-27966A>G		intron_variant	Intron 12 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1470-27966A>G		intron_variant	Intron 12 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.1119-27966A>G		intron_variant	Intron 11 of 14		XP_016861692.1
SLC9A9	XM_011512703.4	c.822-27966A>G		intron_variant	Intron 9 of 12		XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1470-27966A>G		intron_variant	Intron 12 of 15	1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7467 AN: 152182 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.00969

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0344

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0492 AC: 7486 AN: 152300 Hom.: 250 Cov.: 32 AF XY: 0.0466 AC XY: 3469 AN XY: 74482

African (AFR) AF: 0.0891 AC: 3702 AN: 41540

American (AMR) AF: 0.0513 AC: 785 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3470

East Asian (EAS) AF: 0.0397 AC: 206 AN: 5184

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4824

European-Finnish (FIN) AF: 0.00969 AC: 103 AN: 10628

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0344 AC: 2343 AN: 68028

Other (OTH) AF: 0.0535 AC: 113 AN: 2114

Alfa AF: 0.0450 Hom.: 31

Bravo AF: 0.0547

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.55
PhyloP100		0.33
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: rs16853564; hg19: chr3-143128922;