Genetic Variant TEKTIP1:c.322+15_322+18dupCCCC (chr19-3543480-G-GCCCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000329493.6(TEKTIP1):c.322+7_322+8insCCCC variant causes a splice region, 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 0.0079 ( 37 hom., cov: 0)

Exomes 𝑓: 0.00048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TEKTIP1
ENST00000329493.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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

new If you want to explore the variant's impact on the transcript ENST00000329493.6, 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000329493.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKTIP1	NM_001135580.2	MANE Select	c.322+15_322+18dupCCCC		intron	N/A	NP_001129052.1	A6NCJ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TEKTIP1	ENST00000329493.6	TSL:2 MANE Select	c.322+7_322+8insCCCC	splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
MFSD12	ENST00000398558.8	TSL:2	c.329-504_329-503insGGGG	intron	N/A	ENSP00000381566.4	A0A0A0MS91
MFSD12	ENST00000615073.4	TSL:3	c.490+1328_490+1329insGGGG	intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes

AF:

0.00786

AC:

967

AN:

123072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.00279

Gnomad AMR

AF:

0.00287

Gnomad ASJ

AF:

0.00291

Gnomad EAS

AF:

0.000215

Gnomad SAS

AF:

0.00273

Gnomad FIN

AF:

0.00224

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00363

GnomAD2 exomes

AF:

0.000999

AC:

AN:

78042

AF XY:

0.000876

show subpopulations

Gnomad AFR exome

AF:

0.00537

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.000954

Gnomad EAS exome

AF:

0.000504

Gnomad FIN exome

AF:

0.000433

Gnomad NFE exome

AF:

0.000583

Gnomad OTH exome

AF:

0.000406

GnomAD4 exome

AF:

0.000482

AC:

586

AN:

1214996

Hom.:

Cov.:

AF XY:

0.000474

AC XY:

284

AN XY:

599150

show subpopulations

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

African (AFR)

AF:

0.00342

AC:

AN:

28094

American (AMR)

AF:

0.000394

AC:

AN:

33004

Ashkenazi Jewish (ASJ)

AF:

0.000316

AC:

AN:

22124

East Asian (EAS)

AF:

0.0000591

AC:

AN:

33838

South Asian (SAS)

AF:

0.000490

AC:

AN:

71434

European-Finnish (FIN)

AF:

0.0000791

AC:

AN:

37930

Middle Eastern (MID)

AF:

0.00110

AC:

AN:

3624

European-Non Finnish (NFE)

AF:

0.000426

AC:

398

AN:

933318

Other (OTH)

AF:

0.000542

AC:

AN:

51630

⚠️ 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: 0.288

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00786

AC:

967

AN:

123088

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

425

AN XY:

59140

show subpopulations

African (AFR)

AF:

0.0217

AC:

649

AN:

29886

American (AMR)

AF:

0.00287

AC:

AN:

12560

Ashkenazi Jewish (ASJ)

AF:

0.00291

AC:

AN:

3092

East Asian (EAS)

AF:

0.000215

AC:

AN:

4642

South Asian (SAS)

AF:

0.00274

AC:

AN:

3650

European-Finnish (FIN)

AF:

0.00224

AC:

AN:

7596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.00401

AC:

237

AN:

59078

Other (OTH)

AF:

0.00361

AC:

AN:

1660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000712

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.48

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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19-3543480-GCCCCCC-GCCCCCCCCCC

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