3-143268944-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_173653.4(SLC9A9):c.1641G>A(p.Pro547=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,613,366 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (5 hom.)
• Consequence: SLC9A9 NM_173653.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.20

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 3-143268944-C-T is Benign according to our data. Variant chr3-143268944-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 789170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-143268944-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-5.2 with no splicing effect.
• BS2: High AC in GnomAd at 187 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A9	NM_173653.4	c.1641G>A	p.Pro547=	synonymous_variant	15/16	ENST00000316549.11
SLC9A9	XM_017006203.2	c.1290G>A	p.Pro430=	synonymous_variant	14/15
SLC9A9	XM_011512703.4	c.993G>A	p.Pro331=	synonymous_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1641G>A	p.Pro547=	synonymous_variant	15/16	1	NM_173653.4	P1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 187 AN: 151982 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00109 AC: 275 AN: 251382 Hom.: 0 AF XY: 0.00120 AC XY: 163 AN XY: 135842

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00196

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00235 AC: 3431 AN: 1461266 Hom.: 5 Cov.: 31 AF XY: 0.00232 AC XY: 1684 AN XY: 726974

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000812

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.00289

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00123 AC: 187 AN: 152100 Hom.: 0 Cov.: 32 AF XY: 0.000982 AC XY: 73 AN XY: 74356

Gnomad4 AFR AF: 0.000434

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00232

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00184 Hom.: 0

Bravo AF: 0.00139

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	SLC9A9: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Apr 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.16
Dann	Benign	0.44

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: rs61750363; hg19: chr3-142987786; COSMIC: COSV57226177;