chr7-73838650-G-A

Variant names:

• chr7-73838650-G-A
• rs4304218
• NM_152559.3:c.478+1381C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152559.3(METTL27):​c.478+1381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,024 control chromosomes in the GnomAD database, including 30,694 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (30694 hom., cov: 32)
• Consequence: METTL27 NM_152559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL27	NM_152559.3	c.478+1381C>T		intron_variant	Intron 5 of 5	ENST00000297873.9	NP_689772.2
METTL27	XM_017011777.2	c.478+1381C>T		intron_variant	Intron 5 of 5		XP_016867266.1
METTL27	XM_017011778.2	c.478+1381C>T		intron_variant	Intron 5 of 5		XP_016867267.1
METTL27	XR_001744563.2	n.687+210C>T		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL27	ENST00000297873.9	c.478+1381C>T		intron_variant	Intron 5 of 5	1	NM_152559.3	ENSP00000297873.4
METTL27	ENST00000458679.5	n.*69+1381C>T		intron_variant	Intron 4 of 4	4		ENSP00000398533.1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94214 AN: 151906 Hom.: 30673 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.623

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.620 AC: 94275 AN: 152024 Hom.: 30694 Cov.: 32 AF XY: 0.615 AC XY: 45670 AN XY: 74300

African (AFR) AF: 0.421 AC: 17456 AN: 41464

American (AMR) AF: 0.574 AC: 8765 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2279 AN: 3464

East Asian (EAS) AF: 0.598 AC: 3080 AN: 5148

South Asian (SAS) AF: 0.579 AC: 2790 AN: 4820

European-Finnish (FIN) AF: 0.688 AC: 7273 AN: 10574

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50374 AN: 67964

Other (OTH) AF: 0.626 AC: 1322 AN: 2112

Alfa AF: 0.694 Hom.: 16743

Bravo AF: 0.605

Asia WGS AF: 0.582 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.37
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4304218; hg19: chr7-73252980;