Variant 4-68337089-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_StrongBP6_Moderate

The NM_001031732.4(YTHDC1):c.821G>A(p.Gly274Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,744 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

YTHDC1
NM_001031732.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), YTHDC1. . Gene score misZ 2.4773 (greater than the threshold 3.09). Trascript score misZ 3.4335 (greater than threshold 3.09). GenCC has associacion of gene with autism spectrum disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.024259001).

BP6

Variant 4-68337089-C-T is Benign according to our data. Variant chr4-68337089-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2298315.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
YTHDC1	NM_001031732.4 linkuse as main transcript	c.821G>A	p.Gly274Asp	missense_variant	4/17	ENST00000344157.9
YTHDC1	NM_001330698.2 linkuse as main transcript	c.821G>A	p.Gly274Asp	missense_variant	4/17
YTHDC1	NM_133370.4 linkuse as main transcript	c.821G>A	p.Gly274Asp	missense_variant	4/16
YTHDC1	XM_005265708.4 linkuse as main transcript	c.821G>A	p.Gly274Asp	missense_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YTHDC1	ENST00000344157.9 linkuse as main transcript	c.821G>A	p.Gly274Asp	missense_variant	4/17	1	NM_001031732.4	P2	Q96MU7-1
YTHDC1	ENST00000355665.7 linkuse as main transcript	c.821G>A	p.Gly274Asp	missense_variant	4/16	1		A2	Q96MU7-2
YTHDC1	ENST00000579690.5 linkuse as main transcript	c.821G>A	p.Gly274Asp	missense_variant	4/17	5		A2

Frequencies

GnomAD3 genomes

Cov.:

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.0077

T;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.84

T;D;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

N;N;.

MutationTaster

Benign

0.90

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.34

N;N;.

REVEL

Benign

0.069

Sift

Benign

1.0

T;T;.

Sift4G

Benign

0.73

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.029

MVP

0.043

MPC

0.34

ClinPred

0.17

GERP RS

4.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.050

gMVP

0.0067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over