1-26039805-C-G

Position:

• chr1-26039805-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001004434.3(SLC30A2):​c.945G>C​(p.Gln315His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SLC30A2 NM_001004434.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18421683).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A2	NM_001004434.3	c.945G>C	p.Gln315His	missense_variant	7/8	ENST00000374276.4	NP_001004434.1
SLC30A2	NM_032513.5	c.798G>C	p.Gln266His	missense_variant	6/7		NP_115902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A2	ENST00000374276.4	c.945G>C	p.Gln315His	missense_variant	7/8	1	NM_001004434.3	ENSP00000363394.3
SLC30A2	ENST00000374278.7	c.798G>C	p.Gln266His	missense_variant	6/7	1		ENSP00000363396.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461676 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2023

The c.945G>C (p.Q315H) alteration is located in exon 7 (coding exon 7) of the SLC30A2 gene. This alteration results from a G to C substitution at nucleotide position 945, causing the glutamine (Q) at amino acid position 315 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.011
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.22
Sift	Benign	0.057	T;T
Sift4G	Uncertain	0.055	T;T
Polyphen		0.0020	B;B
Vest4		0.27
MutPred		0.40		Loss of catalytic residue at Q266 (P = 0.1163);.;
MVP		0.31
MPC		0.29
ClinPred		0.86	D
GERP RS		3.4
Varity_R		0.22
gMVP		0.80

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

LitVar

Other links and lift over

dbSNP: rs1233216949; hg19: chr1-26366296; COSMIC: COSV100958527; COSMIC: COSV100958527;