rs2166775

Positions:

• chr3-143785691-G-A

Variant summary

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

The NM_173653.4(SLC9A9):​c.533+9310C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,792 control chromosomes in the GnomAD database, including 25,753 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 0.55 (25753 hom., cov: 30)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.533+9310C>T		intron_variant		ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.533+9310C>T		intron_variant			XP_016861691.1
SLC9A9	XM_017006203.2	c.182+9310C>T		intron_variant			XP_016861692.1
SLC9A9	XM_011512704.4	c.533+9310C>T		intron_variant			XP_011511006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.533+9310C>T		intron_variant		1	NM_173653.4	ENSP00000320246.6
SLC9A9	ENST00000474727.2	n.*144+9310C>T		intron_variant		4		ENSP00000419090.2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 83972 AN: 151674 Hom.: 25713 Cov.: 30

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.554 AC: 84070 AN: 151792 Hom.: 25753 Cov.: 30 AF XY: 0.560 AC XY: 41528 AN XY: 74160

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.547

Alfa AF: 0.446 Hom.: 13172

Bravo AF: 0.569

Asia WGS AF: 0.706 AC: 2451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.79

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: rs2166775; hg19: chr3-143504533;