Genetic Variant SLC41A1:p.Leu457Leu (chr1-205791704-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_173854.6(SLC41A1):c.1371G>A(p.Leu457Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000609 in 1,613,756 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L457L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 3 hom. )

Consequence

SLC41A1
NM_173854.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.140

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

kidney disorder
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
nephronophthisis-like nephropathy 2
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

SLC41A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-205791704-C-T is Benign according to our data. Variant chr1-205791704-C-T is described in ClinVar as Benign. ClinVar VariationId is 2044708.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.14 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173854.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A1	NM_173854.6	MANE Select	c.1371G>A	p.Leu457Leu	synonymous	Exon 11 of 11	NP_776253.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC41A1	ENST00000367137.4	TSL:1 MANE Select	c.1371G>A	p.Leu457Leu	synonymous	Exon 11 of 11	ENSP00000356105.3	Q8IVJ1
SLC41A1	ENST00000911130.1		c.1419G>A	p.Leu473Leu	synonymous	Exon 11 of 11	ENSP00000581189.1
SLC41A1	ENST00000948596.1		c.1407G>A	p.Leu469Leu	synonymous	Exon 11 of 11	ENSP00000618655.1

Frequencies

GnomAD3 genomes

AF:

0.00331

AC:

504

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.000988

AC:

246

AN:

248974

AF XY:

0.000719

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000328

AC:

480

AN:

1461502

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

206

AN XY:

727058

show subpopulations

African (AFR)

AF:

0.0112

AC:

374

AN:

33468

American (AMR)

AF:

0.000738

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

1112002

Other (OTH)

AF:

0.000746

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00330

AC:

503

AN:

152254

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0110

AC:

458

AN:

41538

American (AMR)

AF:

0.00222

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00394

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

3.9

(source)

DANN

Benign

0.80

PhyloP100

-0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over