Variant chr7-73840474-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152559.3(METTL27):c.328G>A(p.Gly110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,608,480 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

METTL27
NM_152559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10666022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL27	NM_152559.3 linkuse as main transcript	c.328G>A	p.Gly110Ser	missense_variant	4/6	ENST00000297873.9	NP_689772.2	Q8N6F8
METTL27	XM_017011777.2 linkuse as main transcript	c.328G>A	p.Gly110Ser	missense_variant	4/6		XP_016867266.1
METTL27	XM_017011778.2 linkuse as main transcript	c.328G>A	p.Gly110Ser	missense_variant	4/6		XP_016867267.1
METTL27	XR_001744563.2 linkuse as main transcript	n.359G>A		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.328G>A	p.Gly110Ser	missense_variant	4/6	1	NM_152559.3	ENSP00000297873.4	Q8N6F8
METTL27	ENST00000458679.5 linkuse as main transcript	n.253-354G>A		intron_variant		4		ENSP00000398533.1	B4DWM3
METTL27	ENST00000493174.1 linkuse as main transcript	n.284-354G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000297

AC:

AN:

235884

Hom.:

AF XY:

0.000279

AC XY:

AN XY:

129176

show subpopulations

Gnomad AFR exome

AF:

0.0000705

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.000208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.0000485

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.000197

AC:

287

AN:

1456498

Hom.:

Cov.:

AF XY:

0.000200

AC XY:

145

AN XY:

724264

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00102

Gnomad4 ASJ exome

AF:

0.000577

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000175

Gnomad4 FIN exome

AF:

0.0000385

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.000416

GnomAD4 genome

AF:

0.000197

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000259

Hom.:

Bravo

AF:

0.000291

ExAC

AF:

0.000264

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

Mar 25, 2024

The c.328G>A (p.G110S) alteration is located in exon 4 (coding exon 3) of the WBSCR27 gene. This alteration results from a G to A substitution at nucleotide position 328, causing the glycine (G) at amino acid position 110 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

-0.31

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.54

M_CAP

Benign

0.059

MetaRNN

Benign

0.11

MetaSVM

Uncertain

0.13

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.47

Sift

Benign

0.036

Sift4G

Uncertain

0.039

Polyphen

1.0

Vest4

0.13

MVP

0.74

MPC

0.28

ClinPred

0.092

GERP RS

3.8

Varity_R

0.33

gMVP

0.62

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