3-143708498-C-G

Variant names:

• chr3-143708498-C-G
• rs1122452
• NM_173653.4:c.534-15191G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173653.4(SLC9A9):​c.534-15191G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,954 control chromosomes in the GnomAD database, including 33,137 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 0.66 (33137 hom., cov: 31)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 1 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
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.534-15191G>C		intron_variant	Intron 4 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.534-15191G>C		intron_variant	Intron 4 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.183-15191G>C		intron_variant	Intron 3 of 14		XP_016861692.1
SLC9A9	XM_011512704.4	c.534-15191G>C		intron_variant	Intron 4 of 9		XP_011511006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.534-15191G>C		intron_variant	Intron 4 of 15	1	NM_173653.4	ENSP00000320246.6
SLC9A9	ENST00000474727.2	n.*145-15191G>C		intron_variant	Intron 3 of 3	4		ENSP00000419090.2

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99786 AN: 151836 Hom.: 33110 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.657 AC: 99866 AN: 151954 Hom.: 33137 Cov.: 31 AF XY: 0.652 AC XY: 48406 AN XY: 74258

African (AFR) AF: 0.680 AC: 28167 AN: 41432

American (AMR) AF: 0.640 AC: 9769 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2195 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2099 AN: 5160

South Asian (SAS) AF: 0.590 AC: 2840 AN: 4812

European-Finnish (FIN) AF: 0.685 AC: 7233 AN: 10562

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45577 AN: 67950

Other (OTH) AF: 0.656 AC: 1378 AN: 2102

Alfa AF: 0.578 Hom.: 1789

Bravo AF: 0.656

Asia WGS AF: 0.534 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.79
DANN	Benign	0.78
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1122452; hg19: chr3-143427340;