Genetic Variant TEKTIP1:c.322+17_322+18delCC (chr19-3543480-GCC-G) – 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+8_322+9delCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,336,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00010 ( 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+17_322+18delCC		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+8_322+9delCC	splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
MFSD12	ENST00000398558.8	TSL:2	c.329-505_329-504delGG	intron	N/A	ENSP00000381566.4	A0A0A0MS91
MFSD12	ENST00000615073.4	TSL:3	c.490+1327_490+1328delGG	intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

123118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000159

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000273

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000169

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

122

AN:

1213348

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

598354

show subpopulations

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

African (AFR)

AF:

0.000534

AC:

AN:

28102

American (AMR)

AF:

0.0000606

AC:

AN:

33004

Ashkenazi Jewish (ASJ)

AF:

0.000181

AC:

AN:

22102

East Asian (EAS)

AF:

0.00

AC:

AN:

33804

South Asian (SAS)

AF:

0.000210

AC:

AN:

71386

European-Finnish (FIN)

AF:

0.000106

AC:

AN:

37878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3620

European-Non Finnish (NFE)

AF:

0.0000837

AC:

AN:

931872

Other (OTH)

AF:

0.0000775

AC:

AN:

51580

⚠️ 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: 0.289

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:

0.000146

AC:

AN:

123118

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

AN XY:

59118

show subpopulations

African (AFR)

AF:

0.000469

AC:

AN:

29870

American (AMR)

AF:

0.000159

AC:

AN:

12554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3092

East Asian (EAS)

AF:

0.00

AC:

AN:

4660

South Asian (SAS)

AF:

0.000273

AC:

AN:

3662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.0000169

AC:

AN:

59086

Other (OTH)

AF:

0.00

AC:

AN:

1652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.603

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

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

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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19-3543480-GCCCCCC-GCCCC

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