4-118702312-C-A

Variant names:

• chr4-118702312-C-A
• rs298998
• NM_020961.4:c.739-1623C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020961.4(METTL14):​c.739-1623C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 28)
• Consequence: METTL14 NM_020961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 6 publications found

Genes affected

METTL14 (HGNC:29330): (methyltransferase 14, N6-adenosine-methyltransferase subunit) Enables mRNA binding activity. Contributes to mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity. Involved in mRNA metabolic process; negative regulation of hematopoietic progenitor cell differentiation; and positive regulation of translation. Located in nucleoplasm. Part of RNA N6-methyladenosine methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL14	NM_020961.4	MANE Select	c.739-1623C>A		intron	N/A	NP_066012.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL14	ENST00000388822.10	TSL:1 MANE Select	c.739-1623C>A		intron	N/A	ENSP00000373474.3
	METTL14	ENST00000506780.2	TSL:5	c.205-1623C>A		intron	N/A	ENSP00000424111.2
	METTL14	ENST00000628452.2	TSL:5	n.*470-1623C>A		intron	N/A	ENSP00000486933.1

Frequencies

GnomAD3 genomes Cov.: 28

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.30
PhyloP100		-0.26

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: rs298998; hg19: chr4-119623467;