14-20999754-T-G

Variant names:

• chr14-20999754-T-G
• rs2234632
• NM_014579.4:c.128T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014579.4(SLC39A2):​c.128T>G​(p.Leu43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,613,402 control chromosomes in the GnomAD database, including 391,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43152 hom., cov: 31)
  • Exomes 𝑓: 0.69 (348377 hom.)
• Consequence: SLC39A2 NM_014579.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.419
• Publications: 31 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2318908E-6).
• BP6: Variant 14-20999754-T-G is Benign according to our data. Variant chr14-20999754-T-G is described in ClinVar as Benign. ClinVar VariationId is 1243818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A2	NM_014579.4	c.128T>G	p.Leu43Arg	missense_variant	Exon 2 of 4	ENST00000298681.5	NP_055394.2
SLC39A2	NM_001256588.2	c.128T>G	p.Leu43Arg	missense_variant	Exon 2 of 4		NP_001243517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A2	ENST00000298681.5	c.128T>G	p.Leu43Arg	missense_variant	Exon 2 of 4	1	NM_014579.4	ENSP00000298681.4
SLC39A2	ENST00000554422.5	c.128T>G	p.Leu43Arg	missense_variant	Exon 2 of 4	1		ENSP00000452568.1
SLC39A2	ENST00000554128.1	n.284T>G		non_coding_transcript_exon_variant	Exon 2 of 2	4
ENSG00000258471	ENST00000647921.1	n.474A>C		non_coding_transcript_exon_variant	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113431 AN: 151964 Hom.: 43092 Cov.: 31

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.747

GnomAD2 exomes AF: 0.701 AC: 176168 AN: 251294 AF XY: 0.697

Gnomad AFR exome AF: 0.897

Gnomad AMR exome AF: 0.696

Gnomad ASJ exome AF: 0.751

Gnomad EAS exome AF: 0.725

Gnomad FIN exome AF: 0.718

Gnomad NFE exome AF: 0.679

Gnomad OTH exome AF: 0.694

GnomAD4 exome AF: 0.689 AC: 1006483 AN: 1461322 Hom.: 348377 Cov.: 48 AF XY: 0.687 AC XY: 499300 AN XY: 727002

African (AFR) AF: 0.905 AC: 30280 AN: 33476

American (AMR) AF: 0.703 AC: 31444 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 19581 AN: 26132

East Asian (EAS) AF: 0.739 AC: 29351 AN: 39700

South Asian (SAS) AF: 0.639 AC: 55092 AN: 86234

European-Finnish (FIN) AF: 0.712 AC: 37989 AN: 53384

Middle Eastern (MID) AF: 0.752 AC: 4340 AN: 5768

European-Non Finnish (NFE) AF: 0.680 AC: 755816 AN: 1111526

Other (OTH) AF: 0.705 AC: 42590 AN: 60380

GnomAD4 genome AF: 0.747 AC: 113546 AN: 152080 Hom.: 43152 Cov.: 31 AF XY: 0.747 AC XY: 55544 AN XY: 74320

African (AFR) AF: 0.893 AC: 37058 AN: 41498

American (AMR) AF: 0.737 AC: 11266 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2619 AN: 3468

East Asian (EAS) AF: 0.718 AC: 3702 AN: 5156

South Asian (SAS) AF: 0.639 AC: 3074 AN: 4812

European-Finnish (FIN) AF: 0.714 AC: 7532 AN: 10552

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45842 AN: 67994

Other (OTH) AF: 0.744 AC: 1573 AN: 2114

Alfa AF: 0.702 Hom.: 55285

Bravo AF: 0.765

TwinsUK AF: 0.688 AC: 2551

ALSPAC AF: 0.683 AC: 2632

ESP6500AA AF: 0.913 AC: 4022

ESP6500EA AF: 0.675 AC: 5807

ExAC AF: 0.702 AC: 85183

EpiCase AF: 0.681

EpiControl AF: 0.689

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 25, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26643924) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.9
DANN	Benign	0.54
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.26	T;T
MetaRNN	Benign	0.0000012	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.2	N;N
PhyloP100		0.42
PrimateAI	Benign	0.28	T
PROVEAN	Benign	3.0	N;N
REVEL	Benign	0.063
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.15
MPC		0.043
ClinPred		0.0051	T
GERP RS		2.8
PromoterAI		0.011	Neutral
Varity_R		0.12
gMVP		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2234632; hg19: chr14-21467913; COSMIC: COSV53869131; COSMIC: COSV53869131;