Genetic Variant SLC41A2:c.1175+49_1175+50dupGT (chr12-104866381-T-TAC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001387131.1(SLC41A2):c.1224_1225dupGT(p.Tyr409CysfsTer19) variant causes a frameshift 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 0.034 ( 85 hom., cov: 0)

Exomes 𝑓: 0.024 ( 10 hom. )

Consequence

SLC41A2
NM_001387131.1 frameshift

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

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+49_1175+50dupGT		intron	N/A	NP_001339100.1	Q96JW4
SLC41A2	NM_001387131.1		c.1224_1225dupGT	p.Tyr409CysfsTer19	frameshift	Exon 7 of 7	NP_001374060.1
SLC41A2	NM_001387132.1		c.1224_1225dupGT	p.Tyr409CysfsTer19	frameshift	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+51insGT	intron	N/A	ENSP00000258538.3	Q96JW4
SLC41A2	ENST00000906846.1		c.1175+50_1175+51insGT	intron	N/A	ENSP00000576905.1
SLC41A2	ENST00000906847.1		c.1175+50_1175+51insGT	intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

4808

AN:

140926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0462

Gnomad AMI

AF:

0.00347

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0551

Gnomad EAS

AF:

0.0155

Gnomad SAS

AF:

0.0745

Gnomad FIN

AF:

0.0265

Gnomad MID

AF:

0.0342

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0280

GnomAD2 exomes

AF:

0.0219

AC:

3312

AN:

151248

AF XY:

0.0228

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.0329

Gnomad EAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0239

AC:

30508

AN:

1278850

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

15160

AN XY:

628574

show subpopulations

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

African (AFR)

AF:

0.0393

AC:

1112

AN:

28318

American (AMR)

AF:

0.0119

AC:

377

AN:

31734

Ashkenazi Jewish (ASJ)

AF:

0.0440

AC:

901

AN:

20456

East Asian (EAS)

AF:

0.0111

AC:

398

AN:

35832

South Asian (SAS)

AF:

0.0446

AC:

2499

AN:

56048

European-Finnish (FIN)

AF:

0.0243

AC:

990

AN:

40802

Middle Eastern (MID)

AF:

0.0324

AC:

152

AN:

4692

European-Non Finnish (NFE)

AF:

0.0225

AC:

22679

AN:

1008672

Other (OTH)

AF:

0.0268

AC:

1400

AN:

52296

⚠️ 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: 0.338

Heterozygous variant carriers

1715

3429

5144

6858

8573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1012

2024

3036

4048

5060

<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:

0.0342

AC:

4821

AN:

141018

Hom.:

Cov.:

AF XY:

0.0353

AC XY:

2420

AN XY:

68620

show subpopulations

African (AFR)

AF:

0.0465

AC:

1712

AN:

36806

American (AMR)

AF:

0.0225

AC:

323

AN:

14324

Ashkenazi Jewish (ASJ)

AF:

0.0551

AC:

183

AN:

3324

East Asian (EAS)

AF:

0.0155

AC:

AN:

4710

South Asian (SAS)

AF:

0.0739

AC:

312

AN:

4220

European-Finnish (FIN)

AF:

0.0265

AC:

256

AN:

9662

Middle Eastern (MID)

AF:

0.0333

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.0292

AC:

1896

AN:

64892

Other (OTH)

AF:

0.0277

AC:

AN:

1946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

200

401

601

802

1002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0229

Hom.:

405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism

(source)

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-TACACACACACACACACACACACAC

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