3-143268879-T-A

Variant names:

• chr3-143268879-T-A
• rs761296441
• NM_173653.4:c.1706A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_173653.4(SLC9A9):​c.1706A>T​(p.Tyr569Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00012 in 1,599,686 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SLC9A9 NM_173653.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 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, PanelApp Australia
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173653.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	NM_173653.4	MANE Select	c.1706A>T	p.Tyr569Phe	missense	Exon 15 of 16	NP_775924.1	Q8IVB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	ENST00000316549.11	TSL:1 MANE Select	c.1706A>T	p.Tyr569Phe	missense	Exon 15 of 16	ENSP00000320246.6	Q8IVB4
	SLC9A9	ENST00000900956.1		c.1355A>T	p.Tyr452Phe	missense	Exon 12 of 13	ENSP00000571015.1

Frequencies

GnomAD3 genomes AF: 0.0000727 AC: 11 AN: 151208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000163 AC: 41 AN: 251460 AF XY: 0.000162

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000125 AC: 181 AN: 1448478 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 78 AN XY: 720486

African (AFR) AF: 0.0000303 AC: 1 AN: 33052

American (AMR) AF: 0.0000226 AC: 1 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25636

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38734

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.000154 AC: 170 AN: 1102864

Other (OTH) AF: 0.000135 AC: 8 AN: 59396

GnomAD4 genome AF: 0.0000727 AC: 11 AN: 151208 Hom.: 0 Cov.: 32 AF XY: 0.0000813 AC XY: 6 AN XY: 73824

African (AFR) AF: 0.0000485 AC: 2 AN: 41216

American (AMR) AF: 0.00 AC: 0 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5046

South Asian (SAS) AF: 0.00 AC: 0 AN: 4714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67832

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000226 Hom.: 0

Bravo AF: 0.0000907

ExAC AF: 0.000280 AC: 34

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.17
Sift	Benign	0.039	D
Sift4G	Benign	0.086	T
Polyphen		0.99	D
Vest4		0.63
MVP		0.66
MPC		0.28
ClinPred		0.35	T
GERP RS		4.4
Varity_R		0.35
gMVP		0.42
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs761296441; hg19: chr3-142987721;