chr1-26039173-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004434.3(SLC30A2):​c.1106G>A​(p.Gly369Asp) variant causes a missense 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. 16/21 in silico tools predict a benign 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

Scores

19

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.23
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028727114).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC30A2NM_001004434.3 linkuse as main transcriptc.1106G>A p.Gly369Asp missense_variant 8/8 ENST00000374276.4
SLC30A2NM_032513.5 linkuse as main transcriptc.959G>A p.Gly320Asp missense_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC30A2ENST00000374276.4 linkuse as main transcriptc.1106G>A p.Gly369Asp missense_variant 8/81 NM_001004434.3 P1Q9BRI3-2
SLC30A2ENST00000374278.7 linkuse as main transcriptc.959G>A p.Gly320Asp missense_variant 7/71 Q9BRI3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingDepartment of Pathology and Laboratory Medicine, Sinai Health System-The SLC30A2 p.Gly320Asp variant was not identified in the literature nor was it identified in dbSNP, ClinVar or in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (March 6, 2019, v2.1.1). The p.Gly320 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
15
DANN
Benign
0.76
DEOGEN2
Benign
0.081
T;.
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.029
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.14
N;.
MutationTaster
Benign
0.99
D;D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
2.1
N;N
REVEL
Benign
0.058
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.14
MutPred
0.29
Loss of catalytic residue at G320 (P = 0.0209);.;
MVP
0.068
MPC
0.37
ClinPred
0.19
T
GERP RS
4.6
Varity_R
0.083
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-26365664; API