19-2732990-C-G

Variant names:

• chr19-2732990-C-G
• rs373686133
• NM_144564.5:c.706G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144564.5(SLC39A3):​c.706G>C​(p.Val236Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. V236I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC39A3 NM_144564.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

Genes affected

SLC39A3 (HGNC:17128): (solute carrier family 39 member 3) Predicted to enable zinc ion transmembrane transporter activity. Predicted to be involved in zinc ion transmembrane transport. Predicted to act upstream of or within several processes, including T cell homeostasis; chordate embryonic development; and zinc ion transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267001 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38500732).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144564.5. 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
	SLC39A3	NM_144564.5	MANE Select	c.706G>C	p.Val236Leu	missense	Exon 3 of 3	NP_653165.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A3	ENST00000269740.9	TSL:1 MANE Select	c.706G>C	p.Val236Leu	missense	Exon 3 of 3	ENSP00000269740.3	Q9BRY0-1
	ENSG00000267001	ENST00000586572.1	TSL:4	c.210+4058G>C		intron	N/A	ENSP00000467958.1	K7EQS6
	SLC39A3	ENST00000545664.5	TSL:2	c.706G>C	p.Val236Leu	missense	Exon 3 of 4	ENSP00000445345.1	F5H385

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000436 AC: 1 AN: 229542 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000577

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		4.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.12
Sift	Benign	0.32	T
Sift4G	Benign	0.63	T
Polyphen		0.13	B
Vest4		0.38
MutPred		0.65		Loss of catalytic residue at V236 (P = 0.0602)
MVP		0.40
MPC		0.44
ClinPred		0.42	T
GERP RS		4.7
Varity_R		0.19
gMVP		0.79
Mutation Taster		=88/12	polymorphism

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: rs373686133; hg19: chr19-2732988;