chr3-143266258-G-T

Variant names:

• chr3-143266258-G-T
• rs1046706
• NM_173653.4:c.*444C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.86).
• 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 rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.*444C>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006203.2	c.*444C>A		3_prime_UTR_variant	Exon 15 of 15		XP_016861692.1
SLC9A9	XM_011512703.4	c.*444C>A		3_prime_UTR_variant	Exon 13 of 13		XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.*444C>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_173653.4	ENSP00000320246.6

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

African (AFR) AF: 0.555 AC: 6917 AN: 12466

American (AMR) AF: 0.383 AC: 7355 AN: 19208

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 9350 AN: 14058

East Asian (EAS) AF: 0.0826 AC: 2535 AN: 30694

South Asian (SAS) AF: 0.465 AC: 20825 AN: 44806

European-Finnish (FIN) AF: 0.458 AC: 13601 AN: 29720

Middle Eastern (MID) AF: 0.524 AC: 1533 AN: 2924

European-Non Finnish (NFE) AF: 0.586 AC: 159772 AN: 272876

Other (OTH) AF: 0.535 AC: 14031 AN: 26242

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

African (AFR) AF: 0.562 AC: 23295 AN: 41466

American (AMR) AF: 0.436 AC: 6669 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2313 AN: 3470

East Asian (EAS) AF: 0.0873 AC: 451 AN: 5164

South Asian (SAS) AF: 0.437 AC: 2103 AN: 4814

European-Finnish (FIN) AF: 0.422 AC: 4450 AN: 10534

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40147 AN: 67950

Other (OTH) AF: 0.511 AC: 1080 AN: 2114

Alfa AF: 0.565 Hom.: 44202

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
PhyloP100		0.27
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: rs1046706; hg19: chr3-142985100;