3-143367401-A-G

Variant names:

• chr3-143367401-A-G
• rs4839627
• NM_173653.4:c.1525-3838T>C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1525-3838T>C		intron_variant	Intron 13 of 15	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006202.3	c.1525-3838T>C		intron_variant	Intron 13 of 14		XP_016861691.1
SLC9A9	XM_017006203.2	c.1174-3838T>C		intron_variant	Intron 12 of 14		XP_016861692.1
SLC9A9	XM_011512703.4	c.877-3838T>C		intron_variant	Intron 10 of 12		XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1525-3838T>C		intron_variant	Intron 13 of 15	1	NM_173653.4	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

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.721

Alfa AF: 0.697 Hom.: 8761

Bravo AF: 0.732

Asia WGS AF: 0.933 AC: 3244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs4839627; hg19: chr3-143086243;