Genetic Variant NM_001135580.2:c.322+14_322+18delCCCCC (chr19-3543480-GCCCCC-G) – 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+14_322+18delCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,338,738 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00085 ( 2 hom., cov: 0)

Exomes 𝑓: 0.000077 ( 1 hom. )

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2 link	c.322+14_322+18delCCCCC		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+8_322+12delCCCCC		splice_region_variant, intron_variant	Intron 2 of 3	2	NM_001135580.2	ENSP00000327950.4		A6NCJ1

Frequencies

GnomAD3 genomes

AF:

0.000845

AC:

104

AN:

123130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000239

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000169

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000765

AC:

AN:

1215592

Hom.:

AF XY:

0.0000667

AC XY:

AN XY:

599432

show subpopulations

African (AFR)

AF:

0.00266

AC:

AN:

28154

American (AMR)

AF:

0.000303

AC:

AN:

33012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22134

East Asian (EAS)

AF:

0.00

AC:

AN:

33838

South Asian (SAS)

AF:

0.0000280

AC:

AN:

71462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3624

European-Non Finnish (NFE)

AF:

0.00000214

AC:

AN:

933776

Other (OTH)

AF:

0.0000774

AC:

AN:

51658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.649

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:

0.000853

AC:

105

AN:

123146

Hom.:

Cov.:

AF XY:

0.000794

AC XY:

AN XY:

59168

show subpopulations

African (AFR)

AF:

0.00337

AC:

101

AN:

29928

American (AMR)

AF:

0.000239

AC:

AN:

12568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3092

East Asian (EAS)

AF:

0.00

AC:

AN:

4642

South Asian (SAS)

AF:

0.00

AC:

AN:

3650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0000169

AC:

AN:

59082

Other (OTH)

AF:

0.00

AC:

AN:

1660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.646

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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 v4.3

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