Genetic Variant TEKTIP1:c.322+14_322+18dupCCCCC (chr19-3543480-G-GCCCCC) – 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+8insCCCCC 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 0.0022 ( 19 hom., cov: 0)

Exomes 𝑓: 0.00015 ( 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+14_322+18dupCCCCC		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+8insCCCCC	splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
MFSD12	ENST00000398558.8	TSL:2	c.329-504_329-503insGGGGG	intron	N/A	ENSP00000381566.4	A0A0A0MS91
MFSD12	ENST00000615073.4	TSL:3	c.490+1328_490+1329insGGGGG	intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

276

AN:

123110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00747

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000558

Gnomad ASJ

AF:

0.000647

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000273

Gnomad FIN

AF:

0.000658

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000609

Gnomad OTH

AF:

0.00121

GnomAD2 exomes

AF:

0.000448

AC:

AN:

78042

AF XY:

0.000379

show subpopulations

Gnomad AFR exome

AF:

0.00248

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.000811

GnomAD4 exome

AF:

0.000151

AC:

183

AN:

1215440

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

599352

show subpopulations

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

African (AFR)

AF:

0.00121

AC:

AN:

28136

American (AMR)

AF:

0.000182

AC:

AN:

33010

Ashkenazi Jewish (ASJ)

AF:

0.0000904

AC:

AN:

22134

East Asian (EAS)

AF:

0.0000296

AC:

AN:

33838

South Asian (SAS)

AF:

0.000294

AC:

AN:

71454

European-Finnish (FIN)

AF:

0.0000791

AC:

AN:

37934

Middle Eastern (MID)

AF:

0.000552

AC:

AN:

3624

European-Non Finnish (NFE)

AF:

0.000109

AC:

102

AN:

933664

Other (OTH)

AF:

0.000232

AC:

AN:

51646

⚠️ 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: 0.281

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00224

AC:

276

AN:

123126

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

130

AN XY:

59158

show subpopulations

African (AFR)

AF:

0.00745

AC:

223

AN:

29916

American (AMR)

AF:

0.000557

AC:

AN:

12568

Ashkenazi Jewish (ASJ)

AF:

0.000647

AC:

AN:

3092

East Asian (EAS)

AF:

0.00

AC:

AN:

4640

South Asian (SAS)

AF:

0.000274

AC:

AN:

3650

European-Finnish (FIN)

AF:

0.000658

AC:

AN:

7600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.000609

AC:

AN:

59076

Other (OTH)

AF:

0.00120

AC:

AN:

1660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

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:

0.000305

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-GCCCCCCCCCCC

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