Variant rs530654296 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152559.3(METTL27):c.383C>T(p.Pro128Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,577,730 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 4 hom. )

Consequence

METTL27
NM_152559.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005658567).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL27	NM_152559.3 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 4 of 6	ENST00000297873.9	NP_689772.2	Q8N6F8
METTL27	XM_017011777.2 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 4 of 6		XP_016867266.1
METTL27	XM_017011778.2 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 4 of 6		XP_016867267.1
METTL27	XR_001744563.2 link	n.414C>T		non_coding_transcript_exon_variant	Exon 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
METTL27	ENST00000297873.9 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 4 of 6	1	NM_152559.3	ENSP00000297873.4	Q8N6F8
METTL27	ENST00000458679.5 link	n.253-299C>T		intron_variant	Intron 3 of 4	4		ENSP00000398533.1	B4DWM3
METTL27	ENST00000493174.1 link	n.284-299C>T		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000663

AC:

125

AN:

188444

Hom.:

AF XY:

0.000891

AC XY:

AN XY:

102166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00475

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000127

Gnomad OTH exome

AF:

0.000200

GnomAD4 exome

AF:

0.000334

AC:

476

AN:

1425564

Hom.:

Cov.:

AF XY:

0.000490

AC XY:

346

AN XY:

706082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.0000255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.00540

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.000254

GnomAD4 genome

AF:

0.000164

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000576

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.036

Eigen

Benign

-0.077

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.78

M_CAP

Benign

0.032

MetaRNN

Benign

0.0057

MetaSVM

Benign

-0.87

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.10

Sift

Benign

0.10

Sift4G

Uncertain

0.046

Polyphen

0.97

Vest4

0.28

MVP

0.014

MPC

0.20

ClinPred

0.13

GERP RS

4.9

Varity_R

0.13

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over