rs838598

Positions:

• chr3-143495272-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173653.4(SLC9A9):​c.1203+63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,335,254 control chromosomes in the GnomAD database, including 126,478 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 0.42 (13670 hom., cov: 31)
  • Exomes 𝑓: 0.43 (112808 hom.)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1203+63A>G		intron_variant		ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1203+63A>G		intron_variant			XP_016861691.1
SLC9A9	XM_017006203.2	c.852+63A>G		intron_variant			XP_016861692.1
SLC9A9	XM_011512703.4	c.555+63A>G		intron_variant			XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1203+63A>G		intron_variant		1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64013 AN: 151752 Hom.: 13654 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.433 AC: 512630 AN: 1183384 Hom.: 112808 AF XY: 0.435 AC XY: 261600 AN XY: 601738

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.514

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.422 AC: 64071 AN: 151870 Hom.: 13670 Cov.: 31 AF XY: 0.425 AC XY: 31517 AN XY: 74236

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.414

Alfa AF: 0.422 Hom.: 22872

Bravo AF: 0.410

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs838598; hg19: chr3-143214114; COSMIC: COSV57219503;