6-33202118-C-G

Variant names:

• chr6-33202118-C-G
• rs1547387
• NM_006979.3:c.627C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_006979.3(SLC39A7):​c.627C>G​(p.Ser209Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,612,506 control chromosomes in the GnomAD database, including 10,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.088 (741 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9517 hom.)
• Consequence: SLC39A7 NM_006979.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08
• Publications: 28 publications found

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]

SLC39A7 Gene-Disease associations (from GenCC):

• agammaglobulinemia 9, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• agammaglobulinemia

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-33202118-C-G is Benign according to our data. Variant chr6-33202118-C-G is described in ClinVar as Benign. ClinVar VariationId is 1164496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006979.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A7	NM_006979.3	MANE Select	c.627C>G	p.Ser209Ser	synonymous	Exon 3 of 7	NP_008910.2
	SLC39A7	NM_001077516.2		c.627C>G	p.Ser209Ser	synonymous	Exon 4 of 8	NP_001070984.1
	SLC39A7	NM_001288777.2		c.252C>G	p.Ser84Ser	synonymous	Exon 4 of 8	NP_001275706.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A7	ENST00000374677.8	TSL:1 MANE Select	c.627C>G	p.Ser209Ser	synonymous	Exon 3 of 7	ENSP00000363809.3
	SLC39A7	ENST00000374675.7	TSL:1	c.627C>G	p.Ser209Ser	synonymous	Exon 4 of 8	ENSP00000363807.3
	SLC39A7	ENST00000947913.1		c.654C>G	p.Ser218Ser	synonymous	Exon 3 of 7	ENSP00000617972.1

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13424 AN: 152012 Hom.: 739 Cov.: 32

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0962

GnomAD2 exomes AF: 0.106 AC: 25834 AN: 244624 AF XY: 0.115

Gnomad AFR exome AF: 0.0404

Gnomad AMR exome AF: 0.0553

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.0688

Gnomad FIN exome AF: 0.0674

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.107 AC: 156322 AN: 1460376 Hom.: 9517 Cov.: 32 AF XY: 0.112 AC XY: 81289 AN XY: 726516

African (AFR) AF: 0.0467 AC: 1562 AN: 33472

American (AMR) AF: 0.0574 AC: 2565 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3413 AN: 26132

East Asian (EAS) AF: 0.0581 AC: 2308 AN: 39696

South Asian (SAS) AF: 0.216 AC: 18631 AN: 86226

European-Finnish (FIN) AF: 0.0686 AC: 3591 AN: 52310

Middle Eastern (MID) AF: 0.185 AC: 1065 AN: 5764

European-Non Finnish (NFE) AF: 0.105 AC: 116798 AN: 1111674

Other (OTH) AF: 0.106 AC: 6389 AN: 60380

GnomAD4 genome AF: 0.0883 AC: 13432 AN: 152130 Hom.: 741 Cov.: 32 AF XY: 0.0889 AC XY: 6611 AN XY: 74370

African (AFR) AF: 0.0458 AC: 1898 AN: 41486

American (AMR) AF: 0.0698 AC: 1068 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3470

East Asian (EAS) AF: 0.0575 AC: 297 AN: 5168

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4808

European-Finnish (FIN) AF: 0.0659 AC: 699 AN: 10604

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7534 AN: 67986

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.111 Hom.: 745

Bravo AF: 0.0828

Asia WGS AF: 0.138 AC: 478 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.122

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.5
DANN	Benign	0.76
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs1547387; hg19: chr6-33169895; COSMIC: COSV63399674; COSMIC: COSV63399674;