1-26042626-C-T

Variant names:

• chr1-26042626-C-T
• rs864622019
• NM_001004434.3:c.655G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001004434.3(SLC30A2):​c.655G>A​(p.Ala219Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A2 NM_001004434.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.90
• Publications: 1 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

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.655G>A	p.Ala219Thr	missense	Exon 5 of 8	NP_001004434.1	Q9BRI3-2
	SLC30A2	NM_032513.5		c.508G>A	p.Ala170Thr	missense	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.655G>A	p.Ala219Thr	missense	Exon 5 of 8	ENSP00000363394.3	Q9BRI3-2
	SLC30A2	ENST00000374278.7	TSL:1	c.508G>A	p.Ala170Thr	missense	Exon 4 of 7	ENSP00000363396.3	Q9BRI3-1
	SLC30A2	ENST00000946935.1		c.697G>A	p.Ala233Thr	missense	Exon 5 of 8	ENSP00000616994.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		7.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.82
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.85		Gain of disorder (P = 0.1788)
MVP		0.79
MPC		0.97
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.81
gMVP		0.91
Mutation Taster		=32/68	disease causing

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: rs864622019; hg19: chr1-26369117; COSMIC: COSV65332326; COSMIC: COSV65332326;