chr20-63203062-T-C

Variant names:

• chr20-63203062-T-C
• NM_017798.4:c.878A>G

Variant summary

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

The NM_017798.4(YTHDF1):​c.878A>G​(p.Gln293Arg) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YTHDF1 NM_017798.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65
• Publications: 0 publications found

Genes affected

YTHDF1 (HGNC:15867): (YTH N6-methyladenosine RNA binding protein F1) Enables N6-methyladenosine-containing RNA binding activity and ribosome binding activity. Involved in mRNA destabilization; positive regulation of translational initiation; and stress granule assembly. Located in P-body and cytoplasmic stress granule. [provided by Alliance of Genome Resources, Apr 2022]

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=0.0803211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017798.4. 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
	YTHDF1	NM_017798.4	MANE Select	c.878A>G	p.Gln293Arg	missense	Exon 4 of 5	NP_060268.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YTHDF1	ENST00000370339.8	TSL:1 MANE Select	c.878A>G	p.Gln293Arg	missense	Exon 4 of 5	ENSP00000359364.3	Q9BYJ9-1
	YTHDF1	ENST00000960125.1		c.911A>G	p.Gln304Arg	missense	Exon 4 of 5	ENSP00000630184.1
	YTHDF1	ENST00000370334.4	TSL:3	c.133-6328A>G		intron	N/A	ENSP00000359359.4	Q5JXC6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.71
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.097
Sift	Benign	0.20	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.21		Loss of loop (P = 0.0374)
MVP		0.12
MPC		0.46
ClinPred		0.092	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.22
Mutation Taster		=86/14	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

hg19: chr20-61834414;