3-143823101-G-C

Variant names:

• chr3-143823101-G-C
• rs4839669
• NM_173653.4:c.378+8918C>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.378+8918C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,974 control chromosomes in the GnomAD database, including 26,927 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 0.57 (26927 hom., cov: 31)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.378+8918C>G		intron_variant	Intron 2 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.378+8918C>G		intron_variant	Intron 2 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.27+25047C>G		intron_variant	Intron 1 of 14		XP_016861692.1
SLC9A9	XM_011512704.4	c.378+8918C>G		intron_variant	Intron 2 of 9		XP_011511006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.378+8918C>G		intron_variant	Intron 2 of 15	1	NM_173653.4	ENSP00000320246.6
SLC9A9	ENST00000474151.1	c.378+8918C>G		intron_variant	Intron 2 of 2	4		ENSP00000418627.1
SLC9A9	ENST00000474727.2	n.175+25047C>G		intron_variant	Intron 1 of 3	4		ENSP00000419090.2

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86580 AN: 151856 Hom.: 26924 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.570 AC: 86601 AN: 151974 Hom.: 26927 Cov.: 31 AF XY: 0.571 AC XY: 42413 AN XY: 74316

African (AFR) AF: 0.295 AC: 12214 AN: 41390

American (AMR) AF: 0.603 AC: 9220 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2334 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3219 AN: 5152

South Asian (SAS) AF: 0.576 AC: 2778 AN: 4822

European-Finnish (FIN) AF: 0.715 AC: 7571 AN: 10586

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47097 AN: 67960

Other (OTH) AF: 0.610 AC: 1289 AN: 2112

Alfa AF: 0.619 Hom.: 3817

Bravo AF: 0.551

Asia WGS AF: 0.573 AC: 1996 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	1.8
DANN	Benign	0.72
PhyloP100		0.014
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: rs4839669; hg19: chr3-143541943;