Genetic Variant SLC41A1:p.Arg507Gln (chr1-205791555-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173854.6(SLC41A1):c.1520G>A(p.Arg507Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000101 in 1,613,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

SLC41A1
NM_173854.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18717399).

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.1520G>A	p.Arg507Gln	missense	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.1520G>A	p.Arg507Gln	missense	Exon 11 of 11	ENSP00000356105.3	Q8IVJ1
SLC41A1	ENST00000911130.1		c.1568G>A	p.Arg523Gln	missense	Exon 11 of 11	ENSP00000581189.1
SLC41A1	ENST00000948596.1		c.1556G>A	p.Arg519Gln	missense	Exon 11 of 11	ENSP00000618655.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000517

AC:

AN:

251374

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000106

AC:

155

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000990

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000129

AC:

144

AN:

1112002

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000116

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0090

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

6.1

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Benign

0.27

Sift4G

Benign

0.28

Polyphen

0.53

Vest4

0.51

MutPred

0.27

Loss of phosphorylation at T509 (P = 0.062)

MVP

0.093

MPC

0.82

ClinPred

0.24

GERP RS

5.6

Varity_R

0.13

gMVP

0.73

Mutation Taster

=46/54

disease causing

(source)

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

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