Genetic Variant TEKTIP1:c.322+18delC (chr19-3543480-GC-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001135580.2(TEKTIP1):c.322+18delC 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 0.034 ( 247 hom., cov: 0)

Exomes 𝑓: 0.17 ( 274 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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.097 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.0339

AC:

4160

AN:

122714

Hom.:

245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0999

Gnomad AMI

AF:

0.00418

Gnomad AMR

AF:

0.0193

Gnomad ASJ

AF:

0.0178

Gnomad EAS

AF:

0.0170

Gnomad SAS

AF:

0.0546

Gnomad FIN

AF:

0.00805

Gnomad MID

AF:

0.0310

Gnomad NFE

AF:

0.00818

Gnomad OTH

AF:

0.0298

GnomAD2 exomes

AF:

0.229

AC:

17884

AN:

78042

AF XY:

0.233

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.308

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.168

AC:

171103

AN:

1020834

Hom.:

274

Cov.:

AF XY:

0.170

AC XY:

85562

AN XY:

503588

show subpopulations

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

African (AFR)

AF:

0.162

AC:

4220

AN:

26034

American (AMR)

AF:

0.198

AC:

5185

AN:

26246

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

3458

AN:

19046

East Asian (EAS)

AF:

0.371

AC:

9797

AN:

26404

South Asian (SAS)

AF:

0.142

AC:

8593

AN:

60598

European-Finnish (FIN)

AF:

0.225

AC:

7018

AN:

31168

Middle Eastern (MID)

AF:

0.186

AC:

582

AN:

3122

European-Non Finnish (NFE)

AF:

0.159

AC:

124383

AN:

784408

Other (OTH)

AF:

0.180

AC:

7867

AN:

43808

⚠️ 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: 0.291

Heterozygous variant carriers

16404

32809

49213

65618

82022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4038

8076

12114

16152

20190

<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:

0.0340

AC:

4167

AN:

122728

Hom.:

247

Cov.:

AF XY:

0.0349

AC XY:

2055

AN XY:

58916

show subpopulations

African (AFR)

AF:

0.100

AC:

2991

AN:

29916

American (AMR)

AF:

0.0192

AC:

241

AN:

12532

Ashkenazi Jewish (ASJ)

AF:

0.0178

AC:

AN:

3088

East Asian (EAS)

AF:

0.0170

AC:

AN:

4638

South Asian (SAS)

AF:

0.0546

AC:

199

AN:

3646

European-Finnish (FIN)

AF:

0.00805

AC:

AN:

7450

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.00820

AC:

483

AN:

58880

Other (OTH)

AF:

0.0296

AC:

AN:

1654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

150

300

451

601

751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.104

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 (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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