NM_173653.4:c.1203+63A>G

Variant names:

• chr3-143495272-T-C
• rs838598
• NM_173653.4:c.1203+63A>G

Variant summary

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

The NM_173653.4(SLC9A9):​c.1203+63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,335,254 control chromosomes in the GnomAD database, including 126,478 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 0.42 (13670 hom., cov: 31)
  • Exomes 𝑓: 0.43 (112808 hom.)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1203+63A>G		intron_variant	Intron 10 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1203+63A>G		intron_variant	Intron 10 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.852+63A>G		intron_variant	Intron 9 of 14		XP_016861692.1
SLC9A9	XM_011512703.4	c.555+63A>G		intron_variant	Intron 7 of 12		XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1203+63A>G		intron_variant	Intron 10 of 15	1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64013 AN: 151752 Hom.: 13654 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.433 AC: 512630 AN: 1183384 Hom.: 112808 AF XY: 0.435 AC XY: 261600 AN XY: 601738

African (AFR) AF: 0.376 AC: 10519 AN: 27968

American (AMR) AF: 0.370 AC: 16226 AN: 43826

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 9970 AN: 24254

East Asian (EAS) AF: 0.369 AC: 14095 AN: 38246

South Asian (SAS) AF: 0.461 AC: 36877 AN: 79962

European-Finnish (FIN) AF: 0.514 AC: 26927 AN: 52424

Middle Eastern (MID) AF: 0.338 AC: 1763 AN: 5218

European-Non Finnish (NFE) AF: 0.435 AC: 374481 AN: 860484

Other (OTH) AF: 0.427 AC: 21772 AN: 51002

GnomAD4 genome AF: 0.422 AC: 64071 AN: 151870 Hom.: 13670 Cov.: 31 AF XY: 0.425 AC XY: 31517 AN XY: 74236

African (AFR) AF: 0.381 AC: 15759 AN: 41400

American (AMR) AF: 0.402 AC: 6136 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3464

East Asian (EAS) AF: 0.382 AC: 1973 AN: 5160

South Asian (SAS) AF: 0.441 AC: 2124 AN: 4812

European-Finnish (FIN) AF: 0.522 AC: 5500 AN: 10532

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29676 AN: 67922

Other (OTH) AF: 0.414 AC: 871 AN: 2106

Alfa AF: 0.423 Hom.: 53985

Bravo AF: 0.410

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.53
PhyloP100		-0.30
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: rs838598; hg19: chr3-143214114; COSMIC: COSV57219503;