1-26039829-A-G

Variant names:

• chr1-26039829-A-G
• rs35925054
• NM_001004434.3:c.921T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (18 hom.)
• Consequence: SLC30A2 NM_001004434.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.144
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• zinc deficiency, transient neonatal

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004434.3. 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
	SLC30A2	NM_001004434.3	MANE Select	c.921T>C	p.His307His	synonymous	Exon 7 of 8	NP_001004434.1	Q9BRI3-2
	SLC30A2	NM_032513.5		c.774T>C	p.His258His	synonymous	Exon 6 of 7	NP_115902.1	Q9BRI3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A2	ENST00000374276.4	TSL:1 MANE Select	c.921T>C	p.His307His	synonymous	Exon 7 of 8	ENSP00000363394.3	Q9BRI3-2
	SLC30A2	ENST00000374278.7	TSL:1	c.774T>C	p.His258His	synonymous	Exon 6 of 7	ENSP00000363396.3	Q9BRI3-1
	SLC30A2	ENST00000946935.1		c.963T>C	p.His321His	synonymous	Exon 7 of 8	ENSP00000616994.1

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 334 AN: 152154 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.00221 AC: 555 AN: 251170 AF XY: 0.00229

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 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.: 18 Cov.: 32 AF XY: 0.00400 AC XY: 2912 AN XY: 727188

African (AFR) AF: 0.000597 AC: 20 AN: 33480

American (AMR) AF: 0.000626 AC: 28 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00406 AC: 106 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.000319 AC: 17 AN: 53324

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00501 AC: 5571 AN: 1111980

Other (OTH) AF: 0.00300 AC: 181 AN: 60392

GnomAD4 genome AF: 0.00219 AC: 334 AN: 152272 Hom.: 1 Cov.: 32 AF XY: 0.00185 AC XY: 138 AN XY: 74458

African (AFR) AF: 0.000842 AC: 35 AN: 41570

American (AMR) AF: 0.000850 AC: 13 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00379 AC: 258 AN: 68008

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00349 Hom.: 0

Bravo AF: 0.00227

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.64
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

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: rs35925054; hg19: chr1-26366320;