1-26042708-T-G

Variant names:

• chr1-26042708-T-G
• rs1219015034
• NM_001004434.3:c.573A>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001004434.3(SLC30A2):​c.573A>C​(p.Ile191Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC30A2 NM_001004434.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.003604
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.834
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.834 with no splicing effect.

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.573A>C	p.Ile191Ile	splice_region synonymous	Exon 5 of 8	NP_001004434.1	Q9BRI3-2
	SLC30A2	NM_032513.5		c.426A>C	p.Ile142Ile	splice_region synonymous	Exon 4 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.573A>C	p.Ile191Ile	splice_region synonymous	Exon 5 of 8	ENSP00000363394.3	Q9BRI3-2
	SLC30A2	ENST00000374278.7	TSL:1	c.426A>C	p.Ile142Ile	splice_region synonymous	Exon 4 of 7	ENSP00000363396.3	Q9BRI3-1
	SLC30A2	ENST00000946935.1		c.615A>C	p.Ile205Ile	splice_region synonymous	Exon 5 of 8	ENSP00000616994.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.83
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0036
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.050		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: rs1219015034; hg19: chr1-26369199;