Variant 14-21000992-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014579.4(SLC39A2):c.343T>C(p.Phe115Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,525,850 control chromosomes in the GnomAD database, including 97,895 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.32 ( 8451 hom., cov: 32)

Exomes 𝑓: 0.36 ( 89444 hom. )

Consequence

SLC39A2
NM_014579.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Variant links:

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]

SLC39A2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3463368E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A2	NM_014579.4 linkuse as main transcript	c.343T>C	p.Phe115Leu	missense_variant	4/4	ENST00000298681.5
SLC39A2	NM_001256588.2 linkuse as main transcript	c.*80T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A2	ENST00000298681.5 linkuse as main transcript	c.343T>C	p.Phe115Leu	missense_variant	4/4	1	NM_014579.4	P1	Q9NP94-1
SLC39A2	ENST00000554422.5 linkuse as main transcript	c.*80T>C		3_prime_UTR_variant	4/4	1			Q9NP94-2
	ENST00000647921.1 linkuse as main transcript	n.398-1162A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48303

AN:

151932

Hom.:

8447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.355

GnomAD3 exomes

AF:

0.367

AC:

69296

AN:

189048

Hom.:

13411

AF XY:

0.367

AC XY:

36595

AN XY:

99802

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.413

Gnomad EAS exome

AF:

0.386

Gnomad SAS exome

AF:

0.353

Gnomad FIN exome

AF:

0.385

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.357

AC:

490807

AN:

1373800

Hom.:

89444

Cov.:

AF XY:

0.357

AC XY:

240520

AN XY:

673836

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.318

AC:

48326

AN:

152050

Hom.:

8451

Cov.:

AF XY:

0.324

AC XY:

24083

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.455

Gnomad4 ASJ

AF:

0.420

Gnomad4 EAS

AF:

0.383

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.352

Alfa

AF:

0.348

Hom.:

21458

Bravo

AF:

0.318

TwinsUK

AF:

0.351

AC:

1300

ALSPAC

AF:

0.354

AC:

1365

ESP6500AA

AF:

0.184

AC:

810

ESP6500EA

AF:

0.352

AC:

3024

ExAC

AF:

0.353

AC:

42618

Asia WGS

AF:

0.328

AC:

1139

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.078

DANN

Benign

0.51

DEOGEN2

Benign

0.026

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.47

MetaRNN

Benign

0.00023

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.97

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

1.4

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.014

MutPred

0.58

Loss of catalytic residue at F115 (P = 0.269);

MPC

0.037

ClinPred

0.023

GERP RS

-11

Varity_R

0.086

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over