rs2234632

chr14-20999754-T-Achr14-20999754-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014579.4(SLC39A2):c.128T>A(p.Leu43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,613,950 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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. L43R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0085 (19 hom., cov: 31)
  • Exomes 𝑓: 0.00088 (21 hom.)
• Consequence: SLC39A2 NM_014579.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004229337).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00847 (1289/152124) while in subpopulation AFR AF= 0.0287 (1189/41498). AF 95% confidence interval is 0.0273. There are 19 homozygotes in gnomad4. There are 592 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A2	NM_014579.4	c.128T>A	p.Leu43Gln	missense_variant	2/4	ENST00000298681.5
SLC39A2	NM_001256588.2	c.128T>A	p.Leu43Gln	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A2	ENST00000298681.5	c.128T>A	p.Leu43Gln	missense_variant	2/4	1	NM_014579.4	P1
SLC39A2	ENST00000554422.5	c.128T>A	p.Leu43Gln	missense_variant	2/4	1
	ENST00000647921.1	n.474A>T		non_coding_transcript_exon_variant	2/5
SLC39A2	ENST00000554128.1	n.284T>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.00848 AC: 1289 AN: 152008 Hom.: 19 Cov.: 31

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00210 AC: 527 AN: 251294 Hom.: 8 AF XY: 0.00151 AC XY: 205 AN XY: 135854

Gnomad AFR exome AF: 0.0281

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000881 AC: 1288 AN: 1461826 Hom.: 21 Cov.: 48 AF XY: 0.000762 AC XY: 554 AN XY: 727220

Gnomad4 AFR exome AF: 0.0302

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.000300

Gnomad4 NFE exome AF: 0.0000477

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.00847 AC: 1289 AN: 152124 Hom.: 19 Cov.: 31 AF XY: 0.00796 AC XY: 592 AN XY: 74346

Gnomad4 AFR AF: 0.0287

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0000593 Hom.: 36744

ExAC AF: 0.00278 AC: 337

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	5.4
Dann	Benign	0.39
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.33	T;T
MetaRNN	Benign	0.0042	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.86	N;N
REVEL	Benign	0.046
Sift	Benign	0.14	T;T
Sift4G	Benign	0.091	T;T
Polyphen		0.0	.;B
Vest4		0.17
MVP		0.35
MPC		0.035
ClinPred		0.0078	T
GERP RS		2.8
Varity_R		0.15
gMVP		0.36

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: rs2234632; hg19: chr14-21467913;