7-73840419-G-T

Variant names:

• chr7-73840419-G-T
• rs530654296
• NM_152559.3:c.383C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152559.3(METTL27):​c.383C>A​(p.Pro128Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P128R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: METTL27 NM_152559.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07216519).

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.383C>A	p.Pro128Gln	missense	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.383C>A	p.Pro128Gln	missense	Exon 4 of 6	ENSP00000297873.4	Q8N6F8
	METTL27	ENST00000866837.1		c.383C>A	p.Pro128Gln	missense	Exon 4 of 6	ENSP00000536896.1
	METTL27	ENST00000866839.1		c.383C>A	p.Pro128Gln	missense	Exon 4 of 6	ENSP00000536898.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425566 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 706084

African (AFR) AF: 0.00 AC: 0 AN: 32520

American (AMR) AF: 0.00 AC: 0 AN: 39182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25430

East Asian (EAS) AF: 0.00 AC: 0 AN: 37380

South Asian (SAS) AF: 0.00 AC: 0 AN: 81968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094254

Other (OTH) AF: 0.00 AC: 0 AN: 59024

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.63
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.74	T
Sift4G	Benign	0.50	T
Polyphen		0.20	B
Vest4		0.17
MutPred		0.47		Loss of glycosylation at P128 (P = 0.0426)
MVP		0.014
MPC		0.16
ClinPred		0.27	T
GERP RS		4.9
Varity_R		0.085
gMVP		0.40
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs530654296; hg19: chr7-73254749;