Genetic Variant NM_001352171.3:c.1175+47_1175+50dupGTGT (chr12-104866381-T-TACAC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001352171.3(SLC41A2):c.1175+47_1175+50dupGTGT variant causes a intron 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 0.0053 ( 5 hom., cov: 0)

Exomes 𝑓: 0.0047 ( 2 hom. )

Consequence

SLC41A2
NM_001352171.3 intron

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:

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new If you want to explore the variant's impact on the transcript NM_001352171.3, 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 -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352171.3. 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+47_1175+50dupGTGT		intron	N/A	NP_001339100.1	Q96JW4
SLC41A2	NM_001387131.1		c.1222_1225dupGTGT	p.Tyr409CysfsTer12	frameshift	Exon 7 of 7	NP_001374060.1
SLC41A2	NM_001387132.1		c.1222_1225dupGTGT	p.Tyr409CysfsTer12	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+51insGTGT	intron	N/A	ENSP00000258538.3	Q96JW4
SLC41A2	ENST00000906846.1		c.1175+50_1175+51insGTGT	intron	N/A	ENSP00000576905.1
SLC41A2	ENST00000906847.1		c.1175+50_1175+51insGTGT	intron	N/A	ENSP00000576906.1

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

736

AN:

141004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00792

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00391

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000847

Gnomad SAS

AF:

0.00473

Gnomad FIN

AF:

0.000931

Gnomad MID

AF:

0.00342

Gnomad NFE

AF:

0.00534

Gnomad OTH

AF:

0.00415

GnomAD4 exome

AF:

0.00465

AC:

5977

AN:

1284760

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

2898

AN XY:

631396

show subpopulations

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

African (AFR)

AF:

0.00540

AC:

154

AN:

28524

American (AMR)

AF:

0.00242

AC:

AN:

31788

Ashkenazi Jewish (ASJ)

AF:

0.0000485

AC:

AN:

20610

East Asian (EAS)

AF:

0.000585

AC:

AN:

35882

South Asian (SAS)

AF:

0.00264

AC:

149

AN:

56348

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

40936

Middle Eastern (MID)

AF:

0.00255

AC:

AN:

4698

European-Non Finnish (NFE)

AF:

0.00526

AC:

5328

AN:

1013430

Other (OTH)

AF:

0.00396

AC:

208

AN:

52544

⚠️ 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: 0.324

Heterozygous variant carriers

370

741

1111

1482

1852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

242

484

726

968

1210

<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:

0.00527

AC:

744

AN:

141096

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

354

AN XY:

68670

show subpopulations

African (AFR)

AF:

0.00812

AC:

299

AN:

36836

American (AMR)

AF:

0.00391

AC:

AN:

14326

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3330

East Asian (EAS)

AF:

0.000849

AC:

AN:

4710

South Asian (SAS)

AF:

0.00474

AC:

AN:

4222

European-Finnish (FIN)

AF:

0.000931

AC:

AN:

9666

Middle Eastern (MID)

AF:

0.00370

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.00534

AC:

347

AN:

64926

Other (OTH)

AF:

0.00411

AC:

AN:

1946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

129

161

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:

0.00

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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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