chr7-73840472-G-T

Variant names:

• chr7-73840472-G-T
• rs781789463
• NM_152559.3:c.330C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_152559.3(METTL27):​c.330C>A​(p.Gly110Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,456,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: METTL27 NM_152559.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.12
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-73840472-G-T is Benign according to our data. Variant chr7-73840472-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3771363.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.12 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152559.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL27	NM_152559.3	MANE Select	c.330C>A	p.Gly110Gly	synonymous	Exon 4 of 6	NP_689772.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL27	ENST00000297873.9	TSL:1 MANE Select	c.330C>A	p.Gly110Gly	synonymous	Exon 4 of 6	ENSP00000297873.4	Q8N6F8
	METTL27	ENST00000866837.1		c.330C>A	p.Gly110Gly	synonymous	Exon 4 of 6	ENSP00000536896.1
	METTL27	ENST00000866839.1		c.330C>A	p.Gly110Gly	synonymous	Exon 4 of 6	ENSP00000536898.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000425 AC: 1 AN: 235172 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000566

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1456190 Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4 AN XY: 724104

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 44160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 85468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000721 AC: 8 AN: 1110080

Other (OTH) AF: 0.00 AC: 0 AN: 60086

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.6
DANN	Benign	0.49
PhyloP100		1.1

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: rs781789463; hg19: chr7-73254802;