rs2234636

Positions:

• chr14-21000992-T-A
• chr14-21000992-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014579.4(SLC39A2):​c.343T>A​(p.Phe115Ile) 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. 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. F115L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC39A2 NM_014579.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05181378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A2	NM_014579.4	c.343T>A	p.Phe115Ile	missense_variant	4/4	ENST00000298681.5	NP_055394.2
SLC39A2	NM_001256588.2	c.*80T>A		3_prime_UTR_variant	4/4		NP_001243517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A2	ENST00000298681.5	c.343T>A	p.Phe115Ile	missense_variant	4/4	1	NM_014579.4	ENSP00000298681	P1
SLC39A2	ENST00000554422.5	c.*80T>A		3_prime_UTR_variant	4/4	1		ENSP00000452568
	ENST00000647921.1	n.398-1162A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.2
DANN	Benign	0.85
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.042
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.027	B
Vest4		0.25
MutPred		0.59		Gain of catalytic residue at F115 (P = 0.2255);
MVP		0.11
MPC		0.048
ClinPred		0.090	T
GERP RS		-11
Varity_R		0.11
gMVP		0.30

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: rs2234636; hg19: chr14-21469151;