dbSNP rs228907: TMPRSS6:c.202+1663C>T (chr22-37101553-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001374504.1(TMPRSS6):c.202+1663C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,792 control chromosomes in the GnomAD database, including 8,352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 8352 hom., cov: 31)

Consequence

TMPRSS6
NM_001374504.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.850

Publications

7 publications found

Variant links:

Genes affected

TMPRSS6 (HGNC:16517): (transmembrane serine protease 6) The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

TMPRSS6 Gene-Disease associations (from GenCC):

IRIDA syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen, PanelApp Australia

TMPRSS6 links:

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new If you want to explore the variant's impact on the transcript NM_001374504.1, 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374504.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMPRSS6	NM_001374504.1	MANE Select	c.202+1663C>T	intron	N/A	NP_001361433.1	Q8IU80-1
TMPRSS6	NM_001289000.2		c.202+1663C>T	intron	N/A	NP_001275929.1	Q8IU80-5
TMPRSS6	NM_001289001.2		c.202+1663C>T	intron	N/A	NP_001275930.1	Q8IU80-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMPRSS6	ENST00000676104.1	MANE Select	c.202+1663C>T	intron	N/A	ENSP00000501573.1	Q8IU80-1
TMPRSS6	ENST00000406856.7	TSL:1	c.202+1663C>T	intron	N/A	ENSP00000384964.1	Q8IU80-5
TMPRSS6	ENST00000346753.9	TSL:1	c.202+1663C>T	intron	N/A	ENSP00000334962.6	Q8IU80-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49382

AN:

151674

Hom.:

8337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.304

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.326

AC:

49442

AN:

151792

Hom.:

8352

Cov.:

AF XY:

0.326

AC XY:

24180

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.393

AC:

16245

AN:

41362

American (AMR)

AF:

0.305

AC:

4652

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

743

AN:

3468

East Asian (EAS)

AF:

0.430

AC:

2209

AN:

5134

South Asian (SAS)

AF:

0.409

AC:

1965

AN:

4806

European-Finnish (FIN)

AF:

0.296

AC:

3119

AN:

10550

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19648

AN:

67896

Other (OTH)

AF:

0.307

AC:

647

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1664

3328

4992

6656

8320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.284

Hom.:

12610

Bravo

AF:

0.322

Asia WGS

AF:

0.449

AC:

1562

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.80

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism (auto)

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over