1-100896287-G-C

Variant names:

• chr1-100896287-G-C
• NM_133496.5:c.25G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_133496.5(SLC30A7):​c.25G>C​(p.Asp9His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A7 NM_133496.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.45

Genes affected

SLC30A7 (HGNC:19306): (solute carrier family 30 member 7) Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A7, permit cellular efflux of zinc (Seve et al., 2004 [PubMed 15154973]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A7	NM_133496.5	c.25G>C	p.Asp9His	missense_variant	Exon 1 of 11	ENST00000357650.9	NP_598003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A7	ENST00000357650.9	c.25G>C	p.Asp9His	missense_variant	Exon 1 of 11	1	NM_133496.5	ENSP00000350278.4
SLC30A7	ENST00000370112.8	c.25G>C	p.Asp9His	missense_variant	Exon 1 of 12	1		ENSP00000359130.4
SLC30A7	ENST00000850622.1	n.25G>C		non_coding_transcript_exon_variant	Exon 1 of 13			ENSP00000520907.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.25G>C (p.D9H) alteration is located in exon 1 (coding exon 1) of the SLC30A7 gene. This alteration results from a G to C substitution at nucleotide position 25, causing the aspartic acid (D) at amino acid position 9 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	0.32
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		8.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.26
Sift	Benign	0.068	T;T
Sift4G	Uncertain	0.058	T;T
Polyphen		1.0	D;D
Vest4		0.58
MutPred		0.36		Loss of ubiquitination at K12 (P = 0.0486);Loss of ubiquitination at K12 (P = 0.0486);
MVP		0.82
MPC		0.38
ClinPred		0.92	D
GERP RS		4.9
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.96
Mutation Taster		=56/44	polymorphism

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

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Other links and lift over

hg19: chr1-101361843;