Genetic Variant TEKTIP1:p.Pro177Leu (chr19-3543910-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001135580.2(TEKTIP1):c.530C>T(p.Pro177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,551,136 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

TEKTIP1
NM_001135580.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.329

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06436053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2 link	c.530C>T	p.Pro177Leu	missense_variant	Exon 4 of 4	ENST00000329493.6	NP_001129052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEKTIP1	ENST00000329493.6 link	c.530C>T	p.Pro177Leu	missense_variant	Exon 4 of 4	2	NM_001135580.2	ENSP00000327950.4	A6NCJ1
TEKTIP1	ENST00000681976.1 link	c.371C>T	p.Pro124Leu	missense_variant	Exon 4 of 4			ENSP00000507755.1	A0A804HK34
MFSD12	ENST00000398558.8 link	c.328+899G>A		intron_variant	Intron 3 of 4	2		ENSP00000381566.4	A0A0A0MS91
MFSD12	ENST00000615073.4 link	c.490+899G>A		intron_variant	Intron 4 of 4	3		ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000270

AC:

AN:

155440

Hom.:

AF XY:

0.000279

AC XY:

AN XY:

82372

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000731

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000734

Gnomad SAS exome

AF:

0.000264

Gnomad FIN exome

AF:

0.0000599

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000218

AC:

305

AN:

1398878

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

166

AN XY:

689972

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.000533

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.00207

Gnomad4 SAS exome

AF:

0.000215

Gnomad4 FIN exome

AF:

0.0000408

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.000310

GnomAD4 genome

AF:

0.000144

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000804

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000102

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.530C>T (p.P177L) alteration is located in exon 4 (coding exon 4) of the C19orf71 gene. This alteration results from a C to T substitution at nucleotide position 530, causing the proline (P) at amino acid position 177 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

Eigen

Benign

0.032

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.3

PROVEAN

Pathogenic

-8.8

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.025

Polyphen

0.99

Vest4

0.47

MVP

0.40

ClinPred

0.19

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.61

gMVP

0.14

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