Genetic Variant TEKTIP1:c.322+8_322+18dupCCCCCCCCCCC (chr19-3543480-G-GCCCCCCCCCCC) – 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+8insCCCCCCCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 0)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

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:

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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+8_322+18dupCCCCCCCCCCC		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+8insCCCCCCCCCCC	splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
MFSD12	ENST00000398558.8	TSL:2	c.329-504_329-503insGGGGGGGGGGG	intron	N/A	ENSP00000381566.4	A0A0A0MS91
MFSD12	ENST00000615073.4	TSL:3	c.490+1328_490+1329insGGGGGGGGGGG	intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes

AF:

0.0000162

AC:

AN:

123128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000670

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.23e-7

AC:

AN:

1215598

Hom.:

Cov.:

AF XY:

0.00000167

AC XY:

AN XY:

599434

show subpopulations

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

African (AFR)

AF:

0.0000355

AC:

AN:

28154

American (AMR)

AF:

0.00

AC:

AN:

33012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22134

East Asian (EAS)

AF:

0.00

AC:

AN:

33838

South Asian (SAS)

AF:

0.00

AC:

AN:

71462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3624

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

933782

Other (OTH)

AF:

0.00

AC:

AN:

51658

⚠️ 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: 0.225

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

AF:

0.0000162

AC:

AN:

123144

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

59168

show subpopulations

African (AFR)

AF:

0.0000668

AC:

AN:

29926

American (AMR)

AF:

0.00

AC:

AN:

12568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3092

East Asian (EAS)

AF:

0.00

AC:

AN:

4642

South Asian (SAS)

AF:

0.00

AC:

AN:

3650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59082

Other (OTH)

AF:

0.00

AC:

AN:

1660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.48

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-GCCCCCCCCCCCCCCCCC

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