Genetic Variant TEKTIP1:c.322+18dupC (chr19-3543480-G-GC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001135580.2(TEKTIP1):c.322+18dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.094 ( 1049 hom., cov: 0)

Exomes 𝑓: 0.13 ( 632 hom. )

Consequence

TEKTIP1
NM_001135580.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.478

Publications

3 publications found

Variant links:

Genes affected

TEKTIP1 (HGNC:34496): (tektin bundle interacting protein 1)

TEKTIP1 links:

MFSD12 (HGNC:28299): (major facilitator superfamily domain containing 12) Enables cysteine transmembrane transporter activity. Involved in cysteine transmembrane transport; pigment metabolic process involved in pigmentation; and regulation of melanin biosynthetic process. Located in lysosome and melanosome. Part of late endosome. [provided by Alliance of Genome Resources, Apr 2022]

MFSD12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 19-3543480-G-GC is Benign according to our data. Variant chr19-3543480-G-GC is described in ClinVar as [Benign]. Clinvar id is 403083.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2 link	c.322+18dupC		intron_variant	Intron 2 of 3	ENST00000329493.6	NP_001129052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKTIP1	ENST00000329493.6 link	c.322+7_322+8insC		splice_region_variant, intron_variant	Intron 2 of 3	2	NM_001135580.2	ENSP00000327950.4		A6NCJ1

Frequencies

GnomAD3 genomes

AF:

0.0939

AC:

11542

AN:

122904

Hom.:

1049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.0905

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.0539

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.0885

Gnomad NFE

AF:

0.0843

Gnomad OTH

AF:

0.0875

GnomAD2 exomes

AF:

0.164

AC:

12825

AN:

78042

AF XY:

0.165

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.0952

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.131

AC:

154320

AN:

1180436

Hom.:

632

Cov.:

AF XY:

0.132

AC XY:

76632

AN XY:

582056

show subpopulations

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

African (AFR)

AF:

0.168

AC:

4598

AN:

27392

American (AMR)

AF:

0.115

AC:

3653

AN:

31830

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3033

AN:

21598

East Asian (EAS)

AF:

0.0642

AC:

2131

AN:

33212

South Asian (SAS)

AF:

0.187

AC:

12982

AN:

69396

European-Finnish (FIN)

AF:

0.0907

AC:

3366

AN:

37120

Middle Eastern (MID)

AF:

0.140

AC:

492

AN:

3524

European-Non Finnish (NFE)

AF:

0.130

AC:

117389

AN:

906272

Other (OTH)

AF:

0.133

AC:

6676

AN:

50092

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

5511

11022

16532

22043

27554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4802

9604

14406

19208

24010

<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:

0.0939

AC:

11545

AN:

122922

Hom.:

1049

Cov.:

AF XY:

0.0930

AC XY:

5493

AN XY:

59056

show subpopulations

African (AFR)

AF:

0.114

AC:

3394

AN:

29866

American (AMR)

AF:

0.103

AC:

1290

AN:

12536

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

368

AN:

3088

East Asian (EAS)

AF:

0.0539

AC:

250

AN:

4638

South Asian (SAS)

AF:

0.155

AC:

563

AN:

3640

European-Finnish (FIN)

AF:

0.0626

AC:

474

AN:

7574

Middle Eastern (MID)

AF:

0.0922

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0844

AC:

4977

AN:

59002

Other (OTH)

AF:

0.0877

AC:

145

AN:

1654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

375

750

1124

1499

1874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0667

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.48

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

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.

19-3543480-GCCCCCC-GCCCCCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over