rs370149363

Variant names:

• chr7-73834862-C-A
• rs370149363
• NM_152559.3:c.619G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-73834862-C-A
• chr7-73834862-C-G
• chr7-73834862-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152559.3(METTL27):​c.619G>T​(p.Ala207Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: METTL27 NM_152559.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054417282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL27	NM_152559.3	c.619G>T	p.Ala207Ser	missense_variant	Exon 6 of 6	ENST00000297873.9	NP_689772.2
METTL27	XM_017011777.2	c.697G>T	p.Ala233Ser	missense_variant	Exon 6 of 6		XP_016867266.1
METTL27	XM_017011778.2	c.697G>T	p.Ala233Ser	missense_variant	Exon 6 of 6		XP_016867267.1
METTL27	XR_001744563.2	n.828G>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL27	ENST00000297873.9	c.619G>T	p.Ala207Ser	missense_variant	Exon 6 of 6	1	NM_152559.3	ENSP00000297873.4
METTL27	ENST00000458679.5	n.*288G>T		downstream_gene_variant		4		ENSP00000398533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251214 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135834

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459390 Hom.: 0 Cov.: 89 AF XY: 0.00000413 AC XY: 3 AN XY: 725952

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.8
DANN	Benign	0.91
DEOGEN2	Benign	0.00084	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.014
Sift	Benign	0.94	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.38		Gain of glycosylation at A207 (P = 0.0171);
MVP		0.014
MPC		0.11
ClinPred		0.071	T
Varity_R		0.13
gMVP		0.31

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: rs370149363; hg19: chr7-73249192;