rs35690712

Positions:

• chr6-33201615-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000374677.8(SLC39A7):​c.370G>C​(p.Gly124Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 1,612,224 control chromosomes in the GnomAD database, including 1,244 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. G124G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.029 (120 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1124 hom.)
• Consequence: SLC39A7 ENST00000374677.8 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.806

Genes affected

SLC39A7 (HGNC:4927): (solute carrier family 39 member 7) The protein encoded by this gene transports zinc from the Golgi and endoplasmic reticulum to the cytoplasm. This transport may be important for activation of tyrosine kinases, some of which could be involved in cancer progression. Therefore, modulation of the encoded protein could be useful as a therapeutic agent against cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016112626).
• BP6: Variant 6-33201615-G-C is Benign according to our data. Variant chr6-33201615-G-C is described in ClinVar as [Benign]. Clinvar id is 1167251.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A7	NM_006979.3	c.370G>C	p.Gly124Arg	missense_variant	1/7	ENST00000374677.8	NP_008910.2
SLC39A7	NM_001077516.2	c.370G>C	p.Gly124Arg	missense_variant	2/8		NP_001070984.1
SLC39A7	NM_001288777.2	c.53-146G>C		intron_variant			NP_001275706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A7	ENST00000374677.8	c.370G>C	p.Gly124Arg	missense_variant	1/7	1	NM_006979.3	ENSP00000363809	P1

Frequencies

GnomAD3 genomes AF: 0.0292 AC: 4438 AN: 152126 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00676

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0354 AC: 8828 AN: 249126 Hom.: 283 AF XY: 0.0376 AC XY: 5087 AN XY: 135154

Gnomad AFR exome AF: 0.00807

Gnomad AMR exome AF: 0.0169

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.00873

Gnomad SAS exome AF: 0.0546

Gnomad FIN exome AF: 0.0232

Gnomad NFE exome AF: 0.0371

Gnomad OTH exome AF: 0.0457

GnomAD4 exome AF: 0.0334 AC: 48729 AN: 1459980 Hom.: 1124 Cov.: 33 AF XY: 0.0348 AC XY: 25260 AN XY: 725938

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.0192

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.00439

Gnomad4 SAS exome AF: 0.0513

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.0291 AC: 4436 AN: 152244 Hom.: 120 Cov.: 32 AF XY: 0.0284 AC XY: 2113 AN XY: 74426

Gnomad4 AFR AF: 0.00864

Gnomad4 AMR AF: 0.0284

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00678

Gnomad4 SAS AF: 0.0510

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0416 Hom.: 156

Bravo AF: 0.0276

TwinsUK AF: 0.0318 AC: 118

ALSPAC AF: 0.0296 AC: 114

ESP6500AA AF: 0.00689 AC: 28

ESP6500EA AF: 0.0391 AC: 328

ExAC AF: 0.0354 AC: 4277

Asia WGS AF: 0.0320 AC: 115 AN: 3478

EpiCase AF: 0.0415

EpiControl AF: 0.0433

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0028	T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.082	N
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	0.89	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.56	N;N
REVEL	Benign	0.041
Sift	Uncertain	0.0090	D;D
Sift4G	Benign	0.64	T;T
Polyphen		0.0	B;B
Vest4		0.12
MPC		1.0
ClinPred		0.0054	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.44

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: rs35690712; hg19: chr6-33169392; COSMIC: COSV63400135; COSMIC: COSV63400135;