Variant 7-73840477-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152559.3(METTL27):c.325C>T(p.Pro109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 1,457,486 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

METTL27
NM_152559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.862

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:

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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=0.04654482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL27	NM_152559.3 linkuse as main transcript	c.325C>T	p.Pro109Ser	missense_variant	4/6	ENST00000297873.9	NP_689772.2	Q8N6F8
METTL27	XM_017011777.2 linkuse as main transcript	c.325C>T	p.Pro109Ser	missense_variant	4/6		XP_016867266.1
METTL27	XM_017011778.2 linkuse as main transcript	c.325C>T	p.Pro109Ser	missense_variant	4/6		XP_016867267.1
METTL27	XR_001744563.2 linkuse as main transcript	n.356C>T		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
METTL27	ENST00000297873.9 linkuse as main transcript	c.325C>T	p.Pro109Ser	missense_variant	4/6	1	NM_152559.3	ENSP00000297873.4	Q8N6F8
METTL27	ENST00000458679.5 linkuse as main transcript	n.253-357C>T		intron_variant		4		ENSP00000398533.1	B4DWM3
METTL27	ENST00000493174.1 linkuse as main transcript	n.284-357C>T		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000168

AC:

AN:

238486

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

130494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000378

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000755

AC:

AN:

1457486

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.325C>T (p.P109S) alteration is located in exon 4 (coding exon 3) of the WBSCR27 gene. This alteration results from a C to T substitution at nucleotide position 325, causing the proline (P) at amino acid position 109 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.7

DANN

Benign

0.54

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.55

M_CAP

Benign

0.0083

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

1.5

REVEL

Benign

0.043

Sift

Benign

0.35

Sift4G

Benign

0.77

Polyphen

0.0040

Vest4

0.063

MutPred

0.47

Gain of phosphorylation at P109 (P = 0.1303);

MVP

0.23

MPC

0.12

ClinPred

0.079

GERP RS

2.8

Varity_R

0.055

gMVP

0.29

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