Genetic Variant SLC30A2:p.His307His (chr1-26039829-A-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001004434.3(SLC30A2):c.921T>C(p.His307His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,614,018 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 18 hom. )

Consequence

SLC30A2
NM_001004434.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.144

Variant links:

Genes affected

SLC30A2 (HGNC:11013): (solute carrier family 30 member 2) The protein encoded by this gene is a zinc transporter that acts as a homodimer. The encoded protein plays a role in secreting zinc into breast milk. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

SLC30A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-26039829-A-G is Benign according to our data. Variant chr1-26039829-A-G is described in ClinVar as [Benign]. Clinvar id is 789148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.144 with no splicing effect.

BS2

High AC in GnomAd4 at 334 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A2	NM_001004434.3 link	c.921T>C	p.His307His	synonymous_variant	Exon 7 of 8	ENST00000374276.4	NP_001004434.1	Q9BRI3-2
SLC30A2	NM_032513.5 link	c.774T>C	p.His258His	synonymous_variant	Exon 6 of 7		NP_115902.1	Q9BRI3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A2	ENST00000374276.4 link	c.921T>C	p.His307His	synonymous_variant	Exon 7 of 8	1	NM_001004434.3	ENSP00000363394.3		Q9BRI3-2
SLC30A2	ENST00000374278.7 link	c.774T>C	p.His258His	synonymous_variant	Exon 6 of 7	1		ENSP00000363396.3		Q9BRI3-1

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

334

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00221

AC:

555

AN:

251170

Hom.:

AF XY:

0.00229

AC XY:

311

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00368

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00405

AC:

5926

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

2912

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00406

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000319

Gnomad4 NFE exome

AF:

0.00501

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00219

AC:

334

AN:

152272

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00379

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00349

Hom.:

Bravo

AF:

0.00227

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.6

DANN

Benign

0.64

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over