Variant 7-73834795-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152559.3(METTL27):c.686C>T(p.Pro229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000582 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

METTL27
NM_152559.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.28

Variant links:

Genes affected

METTL27 (HGNC:19068): (methyltransferase like 27) This gene encodes a protein belonging to ubiE/COQ5 methyltransferase family. The gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.22-q11.23. [provided by RefSeq, Jul 2008]

METTL27 links:

METTL27 (HGNC:):

METTL27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0017281771).

BP6

Variant 7-73834795-G-A is Benign according to our data. Variant chr7-73834795-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657570.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL27	NM_152559.3 linkuse as main transcript	c.686C>T	p.Pro229Leu	missense_variant	6/6	ENST00000297873.9	NP_689772.2	Q8N6F8
METTL27	XM_017011777.2 linkuse as main transcript	c.764C>T	p.Pro255Leu	missense_variant	6/6		XP_016867266.1
METTL27	XM_017011778.2 linkuse as main transcript	c.764C>T	p.Pro255Leu	missense_variant	6/6		XP_016867267.1
METTL27	XR_001744563.2 linkuse as main transcript	n.895C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL27	ENST00000297873.9 linkuse as main transcript	c.686C>T	p.Pro229Leu	missense_variant	6/6	1	NM_152559.3	ENSP00000297873.4		Q8N6F8

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000943

AC:

237

AN:

251294

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.000845

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000588

AC:

860

AN:

1461834

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

488

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.000418

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.000525

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000762

Hom.:

Bravo

AF:

0.000472

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000923

AC:

112

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

METTL27: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0010

DANN

Benign

0.89

DEOGEN2

Benign

0.0036

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.44

M_CAP

Benign

0.018

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.29

REVEL

Benign

0.059

Sift

Benign

0.99

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.030

MVP

0.040

MPC

0.12

ClinPred

0.016

GERP RS

-11

Varity_R

0.040

gMVP

0.28

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