chr1-153960180-C-T

Variant names:

• chr1-153960180-C-T
• NM_001271958.2:c.893G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001271958.2(SLC39A1):​c.893G>A​(p.Ser298Asn) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S298R) has been classified 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: 3.14

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17167461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A1	NM_001271958.2	c.893G>A	p.Ser298Asn	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.893G>A	p.Ser298Asn	missense_variant	Exon 4 of 4	1	NM_001271958.2	ENSP00000348535.4
ENSG00000285779	ENST00000648921.1	n.*981G>A		non_coding_transcript_exon_variant	Exon 6 of 6			ENSP00000498105.1
ENSG00000285779	ENST00000648921.1	n.*981G>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

Aug 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.893G>A (p.S298N) 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 893, causing the serine (S) at amino acid position 298 to be replaced by an asparagine (N). 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	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.18	T;T;T;T;T;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.68	.;.;T;.;.;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L;L;L;L;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	.;N;.;N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	.;D;.;D;D;D;D
Sift4G	Benign	0.078	T;T;T;T;T;T;T
Polyphen		0.030	B;B;B;B;B;B;.
Vest4		0.037
MutPred		0.38		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.40
MPC		0.38
ClinPred		0.29	T
GERP RS		4.5
Varity_R		0.20
gMVP		0.22

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: chr1-153932656;