chr3-143367483-C-T

Variant names:

• chr3-143367483-C-T
• rs4839628
• NM_173653.4:c.1525-3920G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_173653.4(SLC9A9):​c.1525-3920G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,184 control chromosomes in the GnomAD database, including 40,845 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 0.72 (40845 hom., cov: 33)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1525-3920G>A		intron_variant	Intron 13 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1525-3920G>A		intron_variant	Intron 13 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.1174-3920G>A		intron_variant	Intron 12 of 14		XP_016861692.1
SLC9A9	XM_011512703.4	c.877-3920G>A		intron_variant	Intron 10 of 12		XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1525-3920G>A		intron_variant	Intron 13 of 15	1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109835 AN: 152066 Hom.: 40785 Cov.: 33

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.723 AC: 109953 AN: 152184 Hom.: 40845 Cov.: 33 AF XY: 0.724 AC XY: 53815 AN XY: 74380

African (AFR) AF: 0.903 AC: 37508 AN: 41560

American (AMR) AF: 0.688 AC: 10524 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2144 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2745 AN: 5168

South Asian (SAS) AF: 0.554 AC: 2677 AN: 4828

European-Finnish (FIN) AF: 0.808 AC: 8551 AN: 10584

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43610 AN: 67970

Other (OTH) AF: 0.709 AC: 1497 AN: 2112

Alfa AF: 0.655 Hom.: 56327

Bravo AF: 0.724

Asia WGS AF: 0.620 AC: 2160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.69
PhyloP100		1.1
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: rs4839628; hg19: chr3-143086325;