20-63196721-C-A

Variant names:

• chr20-63196721-C-A
• rs377660170
• NM_017798.4:c.1667G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017798.4(YTHDF1):​c.1667G>T​(p.Arg556Leu) variant causes a missense change. 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: 32)
• Consequence: YTHDF1 NM_017798.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41397056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YTHDF1	NM_017798.4	c.1667G>T	p.Arg556Leu	missense_variant	Exon 5 of 5	ENST00000370339.8	NP_060268.2
YTHDF1	XM_024451914.2	c.1517G>T	p.Arg506Leu	missense_variant	Exon 4 of 4		XP_024307682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YTHDF1	ENST00000370339.8	c.1667G>T	p.Arg556Leu	missense_variant	Exon 5 of 5	1	NM_017798.4	ENSP00000359364.3
YTHDF1	ENST00000370334.4	c.146G>T	p.Arg49Leu	missense_variant	Exon 4 of 4	3		ENSP00000359359.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.20
Sift	Uncertain	0.028	D;D
Sift4G	Benign	0.075	T;D
Polyphen		0.99	D;.
Vest4		0.60
MutPred		0.29		Gain of ubiquitination at K551 (P = 0.0279);.;
MVP		0.45
MPC		0.66
ClinPred		0.95	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs377660170; hg19: chr20-61828073;