chr1-26045107-T-C

Position:

• chr1-26045107-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001004434.3(SLC30A2):​c.161A>G​(p.His54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC30A2 NM_001004434.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-26045107-T-C is Pathogenic according to our data. Variant chr1-26045107-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 39552.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A2	NM_001004434.3	c.161A>G	p.His54Arg	missense_variant	2/8	ENST00000374276.4	NP_001004434.1
SLC30A2	NM_032513.5	c.161A>G	p.His54Arg	missense_variant	2/7		NP_115902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A2	ENST00000374276.4	c.161A>G	p.His54Arg	missense_variant	2/8	1	NM_001004434.3	ENSP00000363394	P1
SLC30A2	ENST00000374278.7	c.161A>G	p.His54Arg	missense_variant	2/7	1		ENSP00000363396
SLC30A2	ENST00000498060.1	n.345A>G		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Zinc deficiency, transient neonatal Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 22, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Uncertain	2.9	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-6.6	D;D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.37
MutPred		0.40		Loss of methylation at K57 (P = 0.0516);Loss of methylation at K57 (P = 0.0516);
MVP		0.63
MPC		1.1
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.85
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs587776926; hg19: chr1-26371598;