chr7-73840474-C-T

Variant names:

• chr7-73840474-C-T
• rs782511528
• NM_152559.3:c.328G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152559.3(METTL27):​c.328G>A​(p.Gly110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,608,480 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G110G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: METTL27 NM_152559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10666022).

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.328G>A	p.Gly110Ser	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.328G>A	p.Gly110Ser	missense	Exon 4 of 6	ENSP00000297873.4	Q8N6F8
	METTL27	ENST00000866837.1		c.328G>A	p.Gly110Ser	missense	Exon 4 of 6	ENSP00000536896.1
	METTL27	ENST00000866839.1		c.328G>A	p.Gly110Ser	missense	Exon 4 of 6	ENSP00000536898.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 151982 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000297 AC: 70 AN: 235884 AF XY: 0.000279

Gnomad AFR exome AF: 0.0000705

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.000208

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000485

Gnomad NFE exome AF: 0.000249

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.000197 AC: 287 AN: 1456498 Hom.: 1 Cov.: 31 AF XY: 0.000200 AC XY: 145 AN XY: 724264

African (AFR) AF: 0.000150 AC: 5 AN: 33354

American (AMR) AF: 0.00102 AC: 45 AN: 44198

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 15 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39462

South Asian (SAS) AF: 0.000175 AC: 15 AN: 85540

European-Finnish (FIN) AF: 0.0000385 AC: 2 AN: 51932

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5738

European-Non Finnish (NFE) AF: 0.000160 AC: 178 AN: 1110174

Other (OTH) AF: 0.000416 AC: 25 AN: 60112

GnomAD4 genome AF: 0.000197 AC: 30 AN: 151982 Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 12 AN XY: 74226

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.000328 AC: 5 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000215 Hom.: 0

Bravo AF: 0.000291

ExAC AF: 0.000264 AC: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.11	T
MetaSVM	Uncertain	0.13	D
PhyloP100		1.3
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.47
Sift	Benign	0.036	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.13
MVP		0.74
MPC		0.28
ClinPred		0.092	T
GERP RS		3.8
Varity_R		0.33
gMVP		0.62
Mutation Taster		=84/16	polymorphism

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: rs782511528; hg19: chr7-73254804; COSMIC: COSV52895827;