chr6-110358154-G-T

Position:

• chr6-110358154-G-T

Variant summary

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

The NM_001123364.3(METTL24):​c.119C>A​(p.Ser40Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000671 in 1,042,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: METTL24 NM_001123364.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0930

Genes affected

METTL24 (HGNC:21566): (methyltransferase like 24) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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=0.051906526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL24	NM_001123364.3	c.119C>A	p.Ser40Tyr	missense_variant	1/5	ENST00000338882.5
METTL24	NM_001354594.2	c.-333C>A		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL24	ENST00000338882.5	c.119C>A	p.Ser40Tyr	missense_variant	1/5	5	NM_001123364.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000671 AC: 7 AN: 1042516 Hom.: 0 Cov.: 29 AF XY: 0.00000606 AC XY: 3 AN XY: 494878

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000669

Gnomad4 OTH exome AF: 0.00

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

Sep 17, 2021

The c.119C>A (p.S40Y) alteration is located in exon 1 (coding exon 1) of the METTL24 gene. This alteration results from a C to A substitution at nucleotide position 119, causing the serine (S) at amino acid position 40 to be replaced by a tyrosine (Y). 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	0.099
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.3
DANN	Benign	0.70
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.021
Sift	Benign	0.063	T
Sift4G	Uncertain	0.031	D
Polyphen		0.015	B
Vest4		0.092
MutPred		0.17		Loss of glycosylation at S40 (P = 0.005);
MVP		0.040
MPC		0.24
ClinPred		0.029	T
GERP RS		-0.22
Varity_R		0.043
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr6-110679357;