7-73840121-CTGTG-CTGTGTGTG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_152559.3(METTL27):​c.389-5_389-2dupCACA variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

METTL27
NM_152559.3 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.12195122 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
METTL27NM_152559.3 linkc.389-5_389-2dupCACA splice_acceptor_variant, intron_variant Intron 4 of 5 ENST00000297873.9 NP_689772.2 Q8N6F8
METTL27XM_017011777.2 linkc.389-5_389-2dupCACA splice_acceptor_variant, intron_variant Intron 4 of 5 XP_016867266.1
METTL27XM_017011778.2 linkc.389-5_389-2dupCACA splice_acceptor_variant, intron_variant Intron 4 of 5 XP_016867267.1
METTL27XR_001744563.2 linkn.420-5_420-2dupCACA splice_acceptor_variant, intron_variant Intron 4 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
METTL27ENST00000297873.9 linkc.389-2_389-1insCACA splice_acceptor_variant, intron_variant Intron 4 of 5 1 NM_152559.3 ENSP00000297873.4 Q8N6F8
METTL27ENST00000458679.5 linkn.253-2_253-1insCACA splice_acceptor_variant, intron_variant Intron 3 of 4 4 ENSP00000398533.1 B4DWM3
METTL27ENST00000493174.1 linkn.284-2_284-1insCACA splice_acceptor_variant, intron_variant Intron 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1350360
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
669174
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:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs375025208; hg19: chr7-73254451; API