1-153960159-T-C

Position:

• chr1-153960159-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001271958.2(SLC39A1):​c.914A>G​(p.Lys305Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A1 NM_001271958.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A1	NM_001271958.2	c.914A>G	p.Lys305Arg	missense_variant	4/4	ENST00000356205.9	NP_001258887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A1	ENST00000356205.9	c.914A>G	p.Lys305Arg	missense_variant	4/4	1	NM_001271958.2	ENSP00000348535.4
ENSG00000285779	ENST00000648921.1	n.*1002A>G		non_coding_transcript_exon_variant	6/6			ENSP00000498105.1
ENSG00000285779	ENST00000648921.1	n.*1002A>G		3_prime_UTR_variant	6/6			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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.914A>G (p.K305R) alteration is located in exon 5 (coding exon 3) of the SLC39A1 gene. This alteration results from a A to G substitution at nucleotide position 914, causing the lysine (K) at amino acid position 305 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;T;T;T;T;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.68	.;.;T;.;.;.;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	.;N;.;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.12	.;T;.;T;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T;T;T
Polyphen		1.0	D;D;D;D;D;D;.
Vest4		0.091
MutPred		0.75		Loss of ubiquitination at K305 (P = 0.0167);Loss of ubiquitination at K305 (P = 0.0167);Loss of ubiquitination at K305 (P = 0.0167);Loss of ubiquitination at K305 (P = 0.0167);Loss of ubiquitination at K305 (P = 0.0167);Loss of ubiquitination at K305 (P = 0.0167);Loss of ubiquitination at K305 (P = 0.0167);
MVP		0.70
MPC		0.84
ClinPred		0.84	D
GERP RS		5.4
Varity_R		0.14
gMVP		0.88

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: chr1-153932635;