14-21001170-T-G

Variant names:

• chr14-21001170-T-G
• NM_014579.4:c.521T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014579.4(SLC39A2):​c.521T>G​(p.Phe174Cys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC39A2 NM_014579.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

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.521T>G	p.Phe174Cys	missense	Exon 4 of 4	NP_055394.2	Q9NP94-1
	SLC39A2	NM_001256588.2		c.*258T>G		3_prime_UTR	Exon 4 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.521T>G	p.Phe174Cys	missense	Exon 4 of 4	ENSP00000298681.4	Q9NP94-1
	SLC39A2	ENST00000554422.5	TSL:1	c.*258T>G		3_prime_UTR	Exon 4 of 4	ENSP00000452568.1	Q9NP94-2
	ENSG00000258471	ENST00000647921.1		n.398-1340A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.24
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.86		Loss of stability (P = 0.0619)
MVP		0.58
MPC		0.28
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.66
gMVP		0.36
Mutation Taster		=66/34	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: chr14-21469329;