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 NM_001135580.2(TEKTIP1):c.322+16_322+18dupCCC 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 0.024 ( 144 hom., cov: 0)

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

BS2

High Homozygotes in GnomAdExome4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2 link	c.322+16_322+18dupCCC		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+8insCCC		splice_region_variant, intron_variant	Intron 2 of 3	2	NM_001135580.2	ENSP00000327950.4		A6NCJ1

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.329

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 v4.3

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

Publications

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19-3543480-GCCCCCC-GCCCCCCCCC

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