NM_152559.3:c.204T>C

Variant names:

• chr7-73841118-A-G
• rs141564951
• NM_152559.3:c.204T>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152559.3(METTL27):​c.204T>C​(p.Ser68Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: METTL27 NM_152559.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL27	NM_152559.3	c.204T>C	p.Ser68Ser	synonymous_variant	Exon 3 of 6	ENST00000297873.9	NP_689772.2
METTL27	XM_017011777.2	c.204T>C	p.Ser68Ser	synonymous_variant	Exon 3 of 6		XP_016867266.1
METTL27	XM_017011778.2	c.204T>C	p.Ser68Ser	synonymous_variant	Exon 3 of 6		XP_016867267.1
METTL27	XR_001744563.2	n.235T>C		non_coding_transcript_exon_variant	Exon 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL27	ENST00000297873.9	c.204T>C	p.Ser68Ser	synonymous_variant	Exon 3 of 6	1	NM_152559.3	ENSP00000297873.4
METTL27	ENST00000458679.5	n.204T>C		non_coding_transcript_exon_variant	Exon 3 of 5	4		ENSP00000398533.1
METTL27	ENST00000493174.1	n.235T>C		non_coding_transcript_exon_variant	Exon 3 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.68
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs141564951; hg19: chr7-73255448;