Genetic Variant SLC41A2:c.1175+45_1175+50dupGTGTGT (chr12-104866381-T-TACACAC) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001387131.1(SLC41A2):c.1220_1225dupGTGTGT(p.Cys407_Val408dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SLC41A2
NM_001387131.1 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.602

Publications

2 publications found

Variant links:

Genes affected

SLC41A2 (HGNC:31045): (solute carrier family 41 member 2) Predicted to enable inorganic cation transmembrane transporter activity. Predicted to be involved in magnesium ion transmembrane transport. Predicted to act upstream of or within metal ion transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC41A2 links:

ENSG00000286410 (HGNC:):

ENSG00000286410 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001387131.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001387131.1

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387131.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC41A2	NM_001352171.3	MANE Select	c.1175+45_1175+50dupGTGTGT		intron	N/A	NP_001339100.1	Q96JW4
SLC41A2	NM_001387131.1		c.1220_1225dupGTGTGT	p.Cys407_Val408dup	conservative_inframe_insertion	Exon 7 of 7	NP_001374060.1
SLC41A2	NM_001387132.1		c.1220_1225dupGTGTGT	p.Cys407_Val408dup	conservative_inframe_insertion	Exon 8 of 8	NP_001374061.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC41A2	ENST00000258538.8	TSL:1 MANE Select	c.1175+50_1175+51insGTGTGT	intron	N/A	ENSP00000258538.3	Q96JW4
SLC41A2	ENST00000906846.1		c.1175+50_1175+51insGTGTGT	intron	N/A	ENSP00000576905.1
SLC41A2	ENST00000906847.1		c.1175+50_1175+51insGTGTGT	intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

184

AN:

141010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000489

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:

0.0000770

Gnomad OTH

AF:

0.00207

GnomAD4 exome

AF:

0.000116

AC:

149

AN:

1286154

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

632044

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00308

AC:

AN:

28540

American (AMR)

AF:

0.000189

AC:

AN:

31802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20612

East Asian (EAS)

AF:

0.0000279

AC:

AN:

35884

South Asian (SAS)

AF:

0.000319

AC:

AN:

56372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4704

European-Non Finnish (NFE)

AF:

0.0000276

AC:

AN:

1014698

Other (OTH)

AF:

0.000152

AC:

AN:

52598

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.330

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00130

AC:

183

AN:

141102

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

68672

show subpopulations

African (AFR)

AF:

0.00453

AC:

167

AN:

36834

American (AMR)

AF:

0.000489

AC:

AN:

14326

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3330

East Asian (EAS)

AF:

0.00

AC:

AN:

4710

South Asian (SAS)

AF:

0.00

AC:

AN:

4222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.0000770

AC:

AN:

64932

Other (OTH)

AF:

0.00206

AC:

AN:

1946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.00

Hom.:

405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.60

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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12-104866381-TACACACACACACACACACACAC-TACACACACACACACACACACACACACAC

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