chr19-2732941-C-T

Position:

• chr19-2732941-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144564.5(SLC39A3):​c.755G>A​(p.Ser252Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A3 NM_144564.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3391372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A3	NM_144564.5	c.755G>A	p.Ser252Asn	missense_variant	3/3	ENST00000269740.9	NP_653165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A3	ENST00000269740.9	c.755G>A	p.Ser252Asn	missense_variant	3/3	1	NM_144564.5	ENSP00000269740.3
ENSG00000267001	ENST00000586572.1	c.210+4107G>A		intron_variant		4		ENSP00000467958.1
SLC39A3	ENST00000545664.5	c.755G>A	p.Ser252Asn	missense_variant	3/4	2		ENSP00000445345.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.755G>A (p.S252N) alteration is located in exon 3 (coding exon 2) of the SLC39A3 gene. This alteration results from a G to A substitution at nucleotide position 755, causing the serine (S) at amino acid position 252 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	.;T
Eigen	Benign	0.062
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.021	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.88	P;P
Vest4		0.53
MutPred		0.53		Loss of disorder (P = 0.0726);Loss of disorder (P = 0.0726);
MVP		0.43
MPC		0.35
ClinPred		0.58	D
GERP RS		4.7
Varity_R		0.19
gMVP		0.52

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: rs1259460645; hg19: chr19-2732939;