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 NM_001135580.2(TEKTIP1):c.322+15_322+18dupCCCC variant causes a 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
NM_001135580.2 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

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2 link	c.322+15_322+18dupCCCC		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+8insCCCC		splice_region_variant, intron_variant	Intron 2 of 3	2	NM_001135580.2	ENSP00000327950.4		A6NCJ1

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 = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.288

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over