4-68314262-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001031732.4(YTHDC1):​c.2021G>C​(p.Arg674Pro) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R674Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

YTHDC1
NM_001031732.4 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.10
Variant links:
Genes affected
YTHDC1 (HGNC:30626): (YTH N6-methyladenosine RNA binding protein C1) Enables N6-methyladenosine-containing RNA binding activity. Involved in mRNA export from nucleus; mRNA splice site selection; and regulation of gene expression. Located in nuclear speck and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.2760054).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
YTHDC1NM_001031732.4 linkc.2021G>C p.Arg674Pro missense_variant Exon 17 of 17 ENST00000344157.9 NP_001026902.1 Q96MU7-1
YTHDC1NM_001330698.2 linkc.2045G>C p.Arg682Pro missense_variant Exon 17 of 17 NP_001317627.1 Q96MU7J3QR07
YTHDC1NM_133370.4 linkc.1967G>C p.Arg656Pro missense_variant Exon 16 of 16 NP_588611.2 Q96MU7-2
YTHDC1XM_005265708.4 linkc.1991G>C p.Arg664Pro missense_variant Exon 16 of 16 XP_005265765.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
YTHDC1ENST00000344157.9 linkc.2021G>C p.Arg674Pro missense_variant Exon 17 of 17 1 NM_001031732.4 ENSP00000339245.4 Q96MU7-1
YTHDC1ENST00000355665.7 linkc.1967G>C p.Arg656Pro missense_variant Exon 16 of 16 1 ENSP00000347888.3 Q96MU7-2
YTHDC1ENST00000579690.5 linkc.2045G>C p.Arg682Pro missense_variant Exon 17 of 17 5 ENSP00000463982.1 J3QR07

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Uncertain
0.037
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.026
T;.;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.28
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;.;.
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.4
N;N;.
REVEL
Benign
0.18
Sift
Uncertain
0.0070
D;D;.
Sift4G
Benign
0.13
T;T;T
Polyphen
0.98
D;D;.
Vest4
0.57
MutPred
0.23
Loss of methylation at R674 (P = 0.015);.;.;
MVP
0.043
MPC
0.86
ClinPred
0.85
D
GERP RS
4.7
Varity_R
0.59
gMVP
0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751003108; hg19: chr4-69179980; API