3-143266258-G-T

Position:

• chr3-143266258-G-T

Variant summary

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

The NM_173653.4(SLC9A9):​c.*444C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 605,000 control chromosomes in the GnomAD database, including 88,437 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 (22568 hom., cov: 32)
  • Exomes 𝑓: 0.52 (65869 hom.)
• Consequence: SLC9A9 NM_173653.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A9	NM_173653.4	c.*444C>A		3_prime_UTR_variant	16/16	ENST00000316549.11
SLC9A9	XM_011512703.4	c.*444C>A		3_prime_UTR_variant	13/13
SLC9A9	XM_017006203.2	c.*444C>A		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A9	ENST00000316549.11	c.*444C>A		3_prime_UTR_variant	16/16	1	NM_173653.4	P1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81102 AN: 151888 Hom.: 22555 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.521 AC: 235919 AN: 452994 Hom.: 65869 Cov.: 0 AF XY: 0.520 AC XY: 124650 AN XY: 239902

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.0826

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.458

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome AF: 0.534 AC: 81147 AN: 152006 Hom.: 22568 Cov.: 32 AF XY: 0.521 AC XY: 38750 AN XY: 74306

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.0873

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.511

Alfa AF: 0.573 Hom.: 32135

Bravo AF: 0.531

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.39

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: rs1046706; hg19: chr3-142985100;