1-153960346-C-T

Variant names:

• chr1-153960346-C-T
• NM_001271958.2:c.727G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001271958.2(SLC39A1):​c.727G>A​(p.Gly243Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A1 NM_001271958.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

Genes affected

SLC39A1 (HGNC:12876): (solute carrier family 39 member 1) This gene encodes a member of the zinc-iron permease family. The encoded protein is localized to the cell membrane and acts as a zinc uptake transporter. This gene has been linked to prostate cancer, breast cancer, and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ENSG00000285779 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A1	NM_001271958.2	c.727G>A	p.Gly243Arg	missense_variant	Exon 4 of 4	ENST00000356205.9	NP_001258887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A1	ENST00000356205.9	c.727G>A	p.Gly243Arg	missense_variant	Exon 4 of 4	1	NM_001271958.2	ENSP00000348535.4
ENSG00000285779	ENST00000648921.1	n.*815G>A		non_coding_transcript_exon_variant	Exon 6 of 6			ENSP00000498105.1
ENSG00000285779	ENST00000648921.1	n.*815G>A		3_prime_UTR_variant	Exon 6 of 6			ENSP00000498105.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.727G>A (p.G243R) alteration is located in exon 5 (coding exon 3) of the SLC39A1 gene. This alteration results from a G to A substitution at nucleotide position 727, causing the glycine (G) at amino acid position 243 to be replaced by an arginine (R). 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;T;T;T;T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	.;.;D;.;.;.;D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.21	.;N;.;N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.021	.;D;.;D;D;D;D
Sift4G	Benign	0.17	T;T;T;T;T;T;T
Polyphen		0.81	P;P;P;P;P;P;.
Vest4		0.54
MutPred		0.84		Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);
MVP		0.62
MPC		0.54
ClinPred		0.69	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.82

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: chr1-153932822;