7-73834939-T-G

Position:

• chr7-73834939-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152559.3(METTL27):​c.542A>C​(p.Glu181Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: METTL27 NM_152559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66

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]

METTL27 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL27	NM_152559.3	c.542A>C	p.Glu181Ala	missense_variant	6/6	ENST00000297873.9	NP_689772.2
METTL27	XM_017011777.2	c.620A>C	p.Glu207Ala	missense_variant	6/6		XP_016867266.1
METTL27	XM_017011778.2	c.620A>C	p.Glu207Ala	missense_variant	6/6		XP_016867267.1
METTL27	XR_001744563.2	n.751A>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL27	ENST00000297873.9	c.542A>C	p.Glu181Ala	missense_variant	6/6	1	NM_152559.3	ENSP00000297873.4
METTL27	ENST00000458679.5	n.*211A>C		non_coding_transcript_exon_variant	5/5	4		ENSP00000398533.1
METTL27	ENST00000458679.5	n.*211A>C		3_prime_UTR_variant	5/5	4		ENSP00000398533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2023

The c.542A>C (p.E181A) alteration is located in exon 6 (coding exon 5) of the WBSCR27 gene. This alteration results from a A to C substitution at nucleotide position 542, causing the glutamic acid (E) at amino acid position 181 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.78	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.28
Sift	Benign	0.036	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.41		Loss of disorder (P = 0.0738);
MVP		0.28
MPC		0.58
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.34
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-73249269;