3-143268918-C-A

Variant names:

• chr3-143268918-C-A
• NM_173653.4:c.1667G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173653.4(SLC9A9):​c.1667G>T​(p.Cys556Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC9A9 NM_173653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.71

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A9	NM_173653.4	c.1667G>T	p.Cys556Phe	missense_variant	Exon 15 of 16	ENST00000316549.11	NP_775924.1
SLC9A9	XM_017006203.2	c.1316G>T	p.Cys439Phe	missense_variant	Exon 14 of 15		XP_016861692.1
SLC9A9	XM_011512703.4	c.1019G>T	p.Cys340Phe	missense_variant	Exon 12 of 13		XP_011511005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A9	ENST00000316549.11	c.1667G>T	p.Cys556Phe	missense_variant	Exon 15 of 16	1	NM_173653.4	ENSP00000320246.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461566 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.088	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-9.9	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.021	D
Polyphen		0.99	D
Vest4		0.81
MutPred		0.45		Loss of catalytic residue at C556 (P = 0.0186);
MVP		0.85
MPC		0.34
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.90
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-142987760;