chr3-143338537-G-A

Variant names:

• chr3-143338537-G-A
• rs10804689
• NM_173653.4:c.1604+24947C>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.1604+24947C>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 152,036 control chromosomes in the GnomAD database, including 23,243 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 (23243 hom., cov: 32)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 3 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=-0.97).
• 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 rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1604+24947C>T		intron_variant	Intron 14 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1711+24840C>T		intron_variant	Intron 14 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.1253+24947C>T		intron_variant	Intron 13 of 14		XP_016861692.1
SLC9A9	XM_011512703.4	c.956+24947C>T		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+24947C>T		intron_variant	Intron 14 of 15	1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81015 AN: 151918 Hom.: 23210 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.533 AC: 81105 AN: 152036 Hom.: 23243 Cov.: 32 AF XY: 0.530 AC XY: 39413 AN XY: 74316

African (AFR) AF: 0.743 AC: 30815 AN: 41458

American (AMR) AF: 0.538 AC: 8223 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1215 AN: 5160

South Asian (SAS) AF: 0.293 AC: 1412 AN: 4818

European-Finnish (FIN) AF: 0.518 AC: 5479 AN: 10572

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30698 AN: 67958

Other (OTH) AF: 0.523 AC: 1102 AN: 2108

Alfa AF: 0.509 Hom.: 2517

Bravo AF: 0.547

Asia WGS AF: 0.322 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		0.26
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: rs10804689; hg19: chr3-143057379;