3-143367401-A-G

Variant names:

• chr3-143367401-A-G
• rs4839627
• NM_173653.4:c.1525-3838T>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.1525-3838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,096 control chromosomes in the GnomAD database, including 41,097 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 0.73 (41097 hom., cov: 33)
• Consequence: SLC9A9 NM_173653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173653.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	NM_173653.4	MANE Select	c.1525-3838T>C		intron	N/A	NP_775924.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	ENST00000316549.11	TSL:1 MANE Select	c.1525-3838T>C		intron	N/A	ENSP00000320246.6

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111239 AN: 151978 Hom.: 41042 Cov.: 33

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.732 AC: 111352 AN: 152096 Hom.: 41097 Cov.: 33 AF XY: 0.741 AC XY: 55101 AN XY: 74330

African (AFR) AF: 0.743 AC: 30853 AN: 41498

American (AMR) AF: 0.767 AC: 11720 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2480 AN: 3468

East Asian (EAS) AF: 0.996 AC: 5163 AN: 5182

South Asian (SAS) AF: 0.883 AC: 4256 AN: 4820

European-Finnish (FIN) AF: 0.726 AC: 7673 AN: 10568

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46912 AN: 67970

Other (OTH) AF: 0.721 AC: 1521 AN: 2110

Alfa AF: 0.702 Hom.: 15206

Bravo AF: 0.732

Asia WGS AF: 0.933 AC: 3244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.55
PhyloP100		2.2
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: rs4839627; hg19: chr3-143086243;