Genetic Variant TEKTIP1:p.Pro201Leu (chr19-3543982-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001135580.2(TEKTIP1):c.602C>T(p.Pro201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00966 in 1,547,682 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 4 hom., cov: 32)

Exomes 𝑓: 0.010 ( 88 hom. )

Consequence

TEKTIP1
NM_001135580.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.80

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:

ENSG00000267436 (HGNC:56727): (MFSD12 antisense RNA 1)

ENSG00000267436 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038712323).

BP6

Variant 19-3543982-C-T is Benign according to our data. Variant chr19-3543982-C-T is described in ClinVar as [Benign]. Clinvar id is 2648991.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2 link	c.602C>T	p.Pro201Leu	missense_variant	Exon 4 of 4	ENST00000329493.6	NP_001129052.1
MFSD12	NM_174983.5 link	c.*728G>A		downstream_gene_variant		ENST00000355415.7	NP_778148.2	Q6NUT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKTIP1	ENST00000329493.6 link	c.602C>T	p.Pro201Leu	missense_variant	Exon 4 of 4	2	NM_001135580.2	ENSP00000327950.4		A6NCJ1
MFSD12	ENST00000355415.7 link	c.*728G>A		downstream_gene_variant		1	NM_174983.5	ENSP00000347583.1		Q6NUT3-1

Frequencies

GnomAD3 genomes

AF:

0.00605

AC:

920

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00582

AC:

892

AN:

153206

Hom.:

AF XY:

0.00589

AC XY:

477

AN XY:

80924

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.000488

Gnomad EAS exome

AF:

0.000186

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.00645

GnomAD4 exome

AF:

0.0101

AC:

14025

AN:

1395438

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

6842

AN XY:

687892

show subpopulations

Gnomad4 AFR exome

AF:

0.00171

Gnomad4 AMR exome

AF:

0.00419

Gnomad4 ASJ exome

AF:

0.000361

Gnomad4 EAS exome

AF:

0.0000841

Gnomad4 SAS exome

AF:

0.00280

Gnomad4 FIN exome

AF:

0.00224

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.00754

GnomAD4 genome

AF:

0.00604

AC:

920

AN:

152244

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

403

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00846

Hom.:

Bravo

AF:

0.00671

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.0132

AC:

ExAC

AF:

0.00354

AC:

128

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TEKTIP1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.5

DANN

Benign

0.64

DEOGEN2

Benign

0.022

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.018

Sift

Benign

0.37

Sift4G

Benign

1.0

Polyphen

0.014

Vest4

0.15

MVP

0.10

ClinPred

0.0090

GERP RS

-4.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.6

Varity_R

0.054

gMVP

0.068

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over