dbSNP rs145769396: YTHDC1:p.Gly274Val (chr4-68337089-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031732.4(YTHDC1):c.821G>T(p.Gly274Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,900 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

YTHDC1
NM_001031732.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.63

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]

YTHDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.065179765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YTHDC1	NM_001031732.4 link	c.821G>T	p.Gly274Val	missense_variant	Exon 4 of 17	ENST00000344157.9	NP_001026902.1	Q96MU7-1
YTHDC1	NM_001330698.2 link	c.821G>T	p.Gly274Val	missense_variant	Exon 4 of 17		NP_001317627.1	Q96MU7J3QR07
YTHDC1	NM_133370.4 link	c.821G>T	p.Gly274Val	missense_variant	Exon 4 of 16		NP_588611.2	Q96MU7-2
YTHDC1	XM_005265708.4 link	c.821G>T	p.Gly274Val	missense_variant	Exon 4 of 16		XP_005265765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
YTHDC1	ENST00000344157.9 link	c.821G>T	p.Gly274Val	missense_variant	Exon 4 of 17	1	NM_001031732.4	ENSP00000339245.4	Q96MU7-1
YTHDC1	ENST00000355665.7 link	c.821G>T	p.Gly274Val	missense_variant	Exon 4 of 16	1		ENSP00000347888.3	Q96MU7-2
YTHDC1	ENST00000579690.5 link	c.821G>T	p.Gly274Val	missense_variant	Exon 4 of 17	5		ENSP00000463982.1	J3QR07

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251242

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727158

show subpopulations

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Uncertain

DANN

Benign

0.75

DEOGEN2

Benign

0.037

T;.;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.2

N;N;.

REVEL

Benign

0.051

Sift

Benign

0.37

T;T;.

Sift4G

Benign

0.36

T;T;T

Polyphen

0.021

B;B;.

Vest4

0.14

MutPred

0.14

Loss of glycosylation at S273 (P = 0.0343);Loss of glycosylation at S273 (P = 0.0343);Loss of glycosylation at S273 (P = 0.0343);

MVP

0.043

MPC

0.33

ClinPred

0.21

GERP RS

4.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.046

gMVP

0.013

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over