dbSNP rs145769396: YTHDC1:p.Gly274Asp (chr4-68337089-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_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. 15/22 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

YTHDC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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 VariationId is 2298315.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031732.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YTHDC1	NM_001031732.4	MANE Select	c.821G>A	p.Gly274Asp	missense	Exon 4 of 17	NP_001026902.1	Q96MU7-1
YTHDC1	NM_001330698.2		c.821G>A	p.Gly274Asp	missense	Exon 4 of 17	NP_001317627.1	J3QR07
YTHDC1	NM_133370.4		c.821G>A	p.Gly274Asp	missense	Exon 4 of 16	NP_588611.2	Q96MU7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YTHDC1	ENST00000344157.9	TSL:1 MANE Select	c.821G>A	p.Gly274Asp	missense	Exon 4 of 17	ENSP00000339245.4	Q96MU7-1
YTHDC1	ENST00000355665.7	TSL:1	c.821G>A	p.Gly274Asp	missense	Exon 4 of 16	ENSP00000347888.3	Q96MU7-2
YTHDC1	ENST00000936188.1		c.821G>A	p.Gly274Asp	missense	Exon 4 of 18	ENSP00000606247.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251242

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111940

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.84

M_CAP

Benign

0.011

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

PhyloP100

3.6

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.34

REVEL

Benign

0.069

Sift

Benign

1.0

Sift4G

Benign

0.73

Polyphen

0.0

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

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over