14-69442249-A-C

Variant names:

• chr14-69442249-A-C
• rs1262002893
• NM_018375.5:c.386A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018375.5(SLC39A9):​c.386A>C​(p.His129Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H129R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A9 NM_018375.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06
• Publications: 0 publications found

Genes affected

SLC39A9 (HGNC:20182): (solute carrier family 39 member 9) Predicted to enable metal ion transmembrane transporter activity. Predicted to be involved in transmembrane transport and zinc ion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018375.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A9	NM_018375.5	MANE Select	c.386A>C	p.His129Pro	missense	Exon 3 of 7	NP_060845.2
	SLC39A9	NM_001252148.2		c.386A>C	p.His129Pro	missense	Exon 3 of 6	NP_001239077.1	Q9NUM3-2
	SLC39A9	NM_001252150.2		c.386A>C	p.His129Pro	missense	Exon 3 of 7	NP_001239079.1	Q9NUM3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A9	ENST00000336643.10	TSL:1 MANE Select	c.386A>C	p.His129Pro	missense	Exon 3 of 7	ENSP00000336887.5	Q9NUM3-1
	SLC39A9	ENST00000557046.1	TSL:1	c.386A>C	p.His129Pro	missense	Exon 3 of 6	ENSP00000451833.1	Q9NUM3-2
	SLC39A9	ENST00000556605.5	TSL:1	c.386A>C	p.His129Pro	missense	Exon 3 of 7	ENSP00000452385.1	Q9NUM3-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	26
DANN	Benign	0.85
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.41
Sift	Benign	0.067	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.81
MutPred		0.64		Gain of catalytic residue at V130 (P = 0)
MVP		0.41
MPC		2.1
ClinPred		0.96	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.78
gMVP		0.91
Mutation Taster		=10/90	disease causing

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: rs1262002893; hg19: chr14-69908966;