chr14-20999827-A-C

Position:

• chr14-20999827-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014579.4(SLC39A2):​c.201A>C​(p.Glu67Asp) 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. 15/21 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: SLC39A2 NM_014579.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.159

Genes affected

SLC39A2 (HGNC:17127): (solute carrier family 39 member 2) This gene encodes a member of the ZIP family of metal ion transporters. The encoded protein functions as a zinc transporter. Mutations in this gene may be associated with susceptibility to carotid artery disease. Multiple transcript variants have been described. [provided by RefSeq, Mar 2010]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15780783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A2	NM_014579.4	c.201A>C	p.Glu67Asp	missense_variant	2/4	ENST00000298681.5
SLC39A2	NM_001256588.2	c.201A>C	p.Glu67Asp	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A2	ENST00000298681.5	c.201A>C	p.Glu67Asp	missense_variant	2/4	1	NM_014579.4	P1
SLC39A2	ENST00000554422.5	c.201A>C	p.Glu67Asp	missense_variant	2/4	1
	ENST00000647921.1	n.401T>G		non_coding_transcript_exon_variant	2/5
SLC39A2	ENST00000554128.1	n.357A>C		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

Dec 20, 2023

The c.201A>C (p.E67D) alteration is located in exon 2 (coding exon 2) of the SLC39A2 gene. This alteration results from a A to C substitution at nucleotide position 201, causing the glutamic acid (E) at amino acid position 67 to be replaced by an aspartic acid (D). 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	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.038	.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.095
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.73	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.12
Sift	Benign	0.27	T;T
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.43	.;B
Vest4		0.14
MutPred		0.77		Loss of disorder (P = 0.1256);Loss of disorder (P = 0.1256);
MVP		0.26
MPC		0.040
ClinPred		0.78	D
GERP RS		3.3
Varity_R		0.19
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-21467986;