Genetic Variant TEKTIP1:c.322+16_322+18dupCCC (chr19-3543480-G-GCCC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000329493.6(TEKTIP1):c.322+7_322+8insCCC 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 0.024 ( 144 hom., cov: 0)

Exomes 𝑓: 0.0055 ( 17 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 17 gene

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+16_322+18dupCCC		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+8insCCC	splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
MFSD12	ENST00000398558.8	TSL:2	c.329-504_329-503insGGG	intron	N/A	ENSP00000381566.4	A0A0A0MS91
MFSD12	ENST00000615073.4	TSL:3	c.490+1328_490+1329insGGG	intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3003

AN:

122940

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0511

Gnomad AMI

AF:

0.0223

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00129

Gnomad SAS

AF:

0.00984

Gnomad FIN

AF:

0.00605

Gnomad MID

AF:

0.00442

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.0152

GnomAD2 exomes

AF:

0.00826

AC:

645

AN:

78042

AF XY:

0.00767

show subpopulations

Gnomad AFR exome

AF:

0.0450

Gnomad AMR exome

AF:

0.00783

Gnomad ASJ exome

AF:

0.00262

Gnomad EAS exome

AF:

0.000336

Gnomad FIN exome

AF:

0.00260

Gnomad NFE exome

AF:

0.00601

Gnomad OTH exome

AF:

0.00933

GnomAD4 exome

AF:

0.00551

AC:

6685

AN:

1212366

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

3224

AN XY:

597862

show subpopulations

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

African (AFR)

AF:

0.0328

AC:

913

AN:

27822

American (AMR)

AF:

0.00540

AC:

178

AN:

32942

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

22072

East Asian (EAS)

AF:

0.000296

AC:

AN:

33836

South Asian (SAS)

AF:

0.00657

AC:

468

AN:

71208

European-Finnish (FIN)

AF:

0.00309

AC:

117

AN:

37820

Middle Eastern (MID)

AF:

0.00637

AC:

AN:

3612

European-Non Finnish (NFE)

AF:

0.00494

AC:

4598

AN:

931564

Other (OTH)

AF:

0.00598

AC:

308

AN:

51490

⚠️ 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: 0.329

Heterozygous variant carriers

400

800

1201

1601

2001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0244

AC:

3001

AN:

122956

Hom.:

144

Cov.:

AF XY:

0.0233

AC XY:

1378

AN XY:

59080

show subpopulations

African (AFR)

AF:

0.0510

AC:

1522

AN:

29824

American (AMR)

AF:

0.0115

AC:

144

AN:

12534

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3092

East Asian (EAS)

AF:

0.00129

AC:

AN:

4642

South Asian (SAS)

AF:

0.00987

AC:

AN:

3648

European-Finnish (FIN)

AF:

0.00605

AC:

AN:

7598

Middle Eastern (MID)

AF:

0.00485

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0194

AC:

1148

AN:

59038

Other (OTH)

AF:

0.0151

AC:

AN:

1656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

100

200

300

400

500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00605

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 (auto)

(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-GCCCCCCCCC

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