1-153960217-T-G

Variant summary

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

The NM_001271958.2(SLC39A1):c.856A>C(p.Ile286Leu) variant causes a missense change involving the alteration of a non-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: 33)
• Consequence: SLC39A1 NM_001271958.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

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]

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	UniProt
SLC39A1	NM_001271958.2	c.856A>C	p.Ile286Leu	missense_variant	4/4	ENST00000356205.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A1	ENST00000356205.9	c.856A>C	p.Ile286Leu	missense_variant	4/4	1	NM_001271958.2	P1

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

Apr 12, 2023

The c.856A>C (p.I286L) alteration is located in exon 5 (coding exon 3) of the SLC39A1 gene. This alteration results from a A to C substitution at nucleotide position 856, causing the isoleucine (I) at amino acid position 286 to be replaced by a leucine (L). 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	0.73
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
Cadd	Uncertain	26
Dann	Uncertain	0.98
DEOGEN2	Benign	0.23	T;T;T;T;T;T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.74	T
Sift4G	Benign	0.18	T;T;T;T;T;T;T
Polyphen		0.86	P;P;P;P;P;P;.
Vest4		0.34
MutPred		0.73		Loss of helix (P = 0.4763);Loss of helix (P = 0.4763);Loss of helix (P = 0.4763);Loss of helix (P = 0.4763);Loss of helix (P = 0.4763);Loss of helix (P = 0.4763);Loss of helix (P = 0.4763);
MVP		0.53
MPC		0.76
ClinPred		0.83	D
GERP RS		4.2
Varity_R		0.23
gMVP		0.75

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: chr1-153932693;