7-73840045-T-C

Position:

chr7-73840045-T-C

Variant summary

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

The NM_152559.3(METTL27):c.464A>G(p.His155Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,608,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

METTL27
NM_152559.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30

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=0.0518353).

BP6

Variant 7-73840045-T-C is Benign according to our data. Variant chr7-73840045-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3125566.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.464A>G	p.His155Arg	missense_variant	5/6	ENST00000297873.9	NP_689772.2	Q8N6F8
METTL27	XM_017011777.2 linkuse as main transcript	c.464A>G	p.His155Arg	missense_variant	5/6		XP_016867266.1
METTL27	XM_017011778.2 linkuse as main transcript	c.464A>G	p.His155Arg	missense_variant	5/6		XP_016867267.1
METTL27	XR_001744563.2 linkuse as main transcript	n.495A>G		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
METTL27	ENST00000297873.9 linkuse as main transcript	c.464A>G	p.His155Arg	missense_variant	5/6	1	NM_152559.3	ENSP00000297873.4	Q8N6F8
METTL27	ENST00000458679.5 linkuse as main transcript	n.*55A>G		non_coding_transcript_exon_variant	4/5	4		ENSP00000398533.1	B4DWM3
METTL27	ENST00000493174.1 linkuse as main transcript	n.359A>G		non_coding_transcript_exon_variant	4/4	2
METTL27	ENST00000458679.5 linkuse as main transcript	n.*55A>G		3_prime_UTR_variant	4/5	4		ENSP00000398533.1	B4DWM3

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150400

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249400

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134742

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:

0.0000466

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458390

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725374

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:

0.0000233

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150516

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000198

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.1

DANN

Benign

0.74

DEOGEN2

Benign

0.027

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.20

M_CAP

Benign

0.0085

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.34

PROVEAN

Benign

3.7

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.20

MutPred

0.51

Loss of catalytic residue at L154 (P = 0.1043);

MVP

0.040

MPC

0.15

ClinPred

0.023

GERP RS

3.6

Varity_R

0.030

gMVP

0.39

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