rs1501630

Variant names:

• chr3-143325374-C-T
• rs1501630
• NM_173653.4:c.1604+38110G>A

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+38110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,202 control chromosomes in the GnomAD database, including 37,736 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 0.69 (37736 hom., cov: 33)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1604+38110G>A		intron_variant	Intron 14 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1711+38003G>A		intron_variant	Intron 14 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.1253+38110G>A		intron_variant	Intron 13 of 14		XP_016861692.1
SLC9A9	XM_011512703.4	c.956+38110G>A		intron_variant	Intron 11 of 12		XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1604+38110G>A		intron_variant	Intron 14 of 15	1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104629 AN: 152086 Hom.: 37682 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.688 AC: 104736 AN: 152202 Hom.: 37736 Cov.: 33 AF XY: 0.690 AC XY: 51345 AN XY: 74412

African (AFR) AF: 0.910 AC: 37800 AN: 41556

American (AMR) AF: 0.646 AC: 9879 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1973 AN: 3468

East Asian (EAS) AF: 0.430 AC: 2221 AN: 5164

South Asian (SAS) AF: 0.502 AC: 2421 AN: 4824

European-Finnish (FIN) AF: 0.769 AC: 8143 AN: 10592

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40188 AN: 67990

Other (OTH) AF: 0.670 AC: 1413 AN: 2110

Alfa AF: 0.636 Hom.: 13856

Bravo AF: 0.691

Asia WGS AF: 0.527 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.49
DANN	Benign	0.37
PhyloP100		-0.90
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: rs1501630; hg19: chr3-143044216;