Variant 1-205791549-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173854.6(SLC41A1):c.1526C>T(p.Thr509Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC41A1
NM_173854.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

Variant links:

Genes affected

SLC41A1 (HGNC:19429): (solute carrier family 41 member 1) Enables magnesium ion transmembrane transporter activity and magnesium:sodium antiporter activity. Involved in cellular magnesium ion homeostasis; cellular response to magnesium ion; and magnesium ion transmembrane transport. Located in basolateral plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC41A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14633593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC41A1	NM_173854.6 linkuse as main transcript	c.1526C>T	p.Thr509Met	missense_variant	11/11	ENST00000367137.4
SLC41A1	XM_047416887.1 linkuse as main transcript	c.1526C>T	p.Thr509Met	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC41A1	ENST00000367137.4 linkuse as main transcript	c.1526C>T	p.Thr509Met	missense_variant	11/11	1	NM_173854.6	P1
SLC41A1	ENST00000468057.5 linkuse as main transcript	n.1322C>T		non_coding_transcript_exon_variant	10/10	2
SLC41A1	ENST00000484228.1 linkuse as main transcript	n.1592C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251392

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Apr 09, 2023

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 509 of the SLC41A1 protein (p.Thr509Met). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬† is likely to be tolerated. This variant has not been reported in the literature in individuals affected with SLC41A1-related conditions. This variant is present in population databases (rs753516125, gnomAD 0.002%). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.75

M_CAP

Benign

0.0050

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.4

REVEL

Benign

0.070

Sift

Benign

0.12

Sift4G

Benign

0.14

Polyphen

0.26

Vest4

0.12

MutPred

0.18

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.043

MPC

0.54

ClinPred

0.35

GERP RS

5.6

Varity_R

0.074

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over