Variant chr1-153960180-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001271958.2(SLC39A1):c.893G>C(p.Ser298Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SLC39A1
NM_001271958.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.14

Variant links:

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]

SLC39A1 links:

ENSG00000285779 (HGNC:):

ENSG00000285779 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.132272).

BP6

Variant 1-153960180-C-G is Benign according to our data. Variant chr1-153960180-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2242965.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A1	NM_001271958.2 linkuse as main transcript	c.893G>C	p.Ser298Thr	missense_variant	4/4	ENST00000356205.9	NP_001258887.1	Q9NY26-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC39A1	ENST00000356205.9 linkuse as main transcript	c.893G>C	p.Ser298Thr	missense_variant	4/4	1	NM_001271958.2	ENSP00000348535.4	Q9NY26-1
ENSG00000285779	ENST00000648921.1 linkuse as main transcript	n.*981G>C		non_coding_transcript_exon_variant	6/6			ENSP00000498105.1	A0A3B3ITX8
ENSG00000285779	ENST00000648921.1 linkuse as main transcript	n.*981G>C		3_prime_UTR_variant	6/6			ENSP00000498105.1	A0A3B3ITX8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.21

T;T;T;T;T;T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.54

.;.;T;.;.;.;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.13

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;L;L;L;L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

.;N;.;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.30

.;T;.;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B;B;.

Vest4

0.029

MutPred

0.45

Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);

MVP

0.46

MPC

0.28

ClinPred

0.16

GERP RS

4.5

Varity_R

0.12

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over