3-143382098-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_173653.4(SLC9A9):c.1486G>A(p.Asp496Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0013 in 1,614,100 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (10 hom.)
• Consequence: SLC9A9 NM_173653.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.67

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-AS2 (HGNC:40929): (SLC9A9 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010417581).
• BP6: Variant 3-143382098-C-T is Benign according to our data. Variant chr3-143382098-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 252794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 99 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A9	NM_173653.4	c.1486G>A	p.Asp496Asn	missense_variant	13/16	ENST00000316549.11
SLC9A9	XM_017006202.3	c.1486G>A	p.Asp496Asn	missense_variant	13/15
SLC9A9	XM_017006203.2	c.1135G>A	p.Asp379Asn	missense_variant	12/15
SLC9A9	XM_011512703.4	c.838G>A	p.Asp280Asn	missense_variant	10/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1486G>A	p.Asp496Asn	missense_variant	13/16	1	NM_173653.4	P1
SLC9A9-AS2	ENST00000490153.1	n.264C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00103 AC: 260 AN: 251450 Hom.: 3 AF XY: 0.00121 AC XY: 165 AN XY: 135892

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.00353

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.00136 AC: 1995 AN: 1461840 Hom.: 10 Cov.: 31 AF XY: 0.00139 AC XY: 1010 AN XY: 727218

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00376

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00139

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74456

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00106 Hom.: 0

Bravo AF: 0.000608

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00104 AC: 126

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Nov 06, 2015

- -

Autism, susceptibility to, 16 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.61
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.052
Sift	Benign	0.090	T
Sift4G	Benign	0.17	T
Polyphen		0.023	B
Vest4		0.44
MVP		0.47
MPC		0.044
ClinPred		0.048	T
GERP RS		5.1
Varity_R		0.18
gMVP		0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs111291437; hg19: chr3-143100940;