chr14-20999827-A-C

Variant names:

• chr14-20999827-A-C
• NM_014579.4:c.201A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

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]

ENSG00000258471 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014579.4. 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
	SLC39A2	NM_014579.4	MANE Select	c.201A>C	p.Glu67Asp	missense	Exon 2 of 4	NP_055394.2	Q9NP94-1
	SLC39A2	NM_001256588.2		c.201A>C	p.Glu67Asp	missense	Exon 2 of 4	NP_001243517.1	Q9NP94-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A2	ENST00000298681.5	TSL:1 MANE Select	c.201A>C	p.Glu67Asp	missense	Exon 2 of 4	ENSP00000298681.4	Q9NP94-1
	SLC39A2	ENST00000554422.5	TSL:1	c.201A>C	p.Glu67Asp	missense	Exon 2 of 4	ENSP00000452568.1	Q9NP94-2
	SLC39A2	ENST00000554128.1	TSL:4	n.357A>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.16
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.12
Sift	Benign	0.27	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.43	B
Vest4		0.14
MutPred		0.77		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
Mutation Taster		=87/13	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

hg19: chr14-21467986;