6-149683498-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004690.4(LATS1):c.1591C>T(p.Pro531Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00719 in 1,614,200 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 58 hom. )

Consequence

LATS1
NM_004690.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

LATS1 (HGNC:6514): (large tumor suppressor kinase 1) The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments. [provided by RefSeq, Apr 2017]

LATS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005334854).

BP6

Variant 6-149683498-G-A is Benign according to our data. Variant chr6-149683498-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 719906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 713 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LATS1	NM_004690.4 link	c.1591C>T	p.Pro531Ser	missense_variant	Exon 4 of 8	ENST00000543571.6	NP_004681.1	O95835-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LATS1	ENST00000543571.6 link	c.1591C>T	p.Pro531Ser	missense_variant	Exon 4 of 8	1	NM_004690.4	ENSP00000437550.1		O95835-1

Frequencies

GnomAD3 genomes

AF:

0.00468

AC:

713

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00462

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00780

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00414

AC:

1040

AN:

251482

Hom.:

AF XY:

0.00397

AC XY:

539

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.00711

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00745

AC:

10890

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00715

AC XY:

5199

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00354

Gnomad4 NFE exome

AF:

0.00904

Gnomad4 OTH exome

AF:

0.00763

GnomAD4 genome

AF:

0.00468

AC:

713

AN:

152316

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

342

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00462

Gnomad4 NFE

AF:

0.00780

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00645

Hom.:

Bravo

AF:

0.00424

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00380

AC:

461

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00736

EpiControl

AF:

0.00664

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;T;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

.;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.081

T;T;T

Polyphen

0.0050

B;B;B

Vest4

0.21

MVP

0.71

MPC

0.096

ClinPred

0.021

GERP RS

5.5

Varity_R

0.087

gMVP

0.17

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