Variant 4-68337208-TTCC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001031732.4(YTHDC1):c.699_701del(p.Glu249del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,589,110 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 9 hom. )

Consequence

YTHDC1
NM_001031732.4 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.16

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 -5 ACMG points.

BP6

Variant 4-68337208-TTCC-T is Benign according to our data. Variant chr4-68337208-TTCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3053679.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
YTHDC1	NM_001031732.4 linkuse as main transcript	c.699_701del	p.Glu249del	inframe_deletion	4/17	ENST00000344157.9
YTHDC1	NM_001330698.2 linkuse as main transcript	c.699_701del	p.Glu249del	inframe_deletion	4/17
YTHDC1	NM_133370.4 linkuse as main transcript	c.699_701del	p.Glu249del	inframe_deletion	4/16
YTHDC1	XM_005265708.4 linkuse as main transcript	c.699_701del	p.Glu249del	inframe_deletion	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YTHDC1	ENST00000344157.9 linkuse as main transcript	c.699_701del	p.Glu249del	inframe_deletion	4/17	1	NM_001031732.4	P2	Q96MU7-1
YTHDC1	ENST00000355665.7 linkuse as main transcript	c.699_701del	p.Glu249del	inframe_deletion	4/16	1		A2	Q96MU7-2
YTHDC1	ENST00000579690.5 linkuse as main transcript	c.699_701del	p.Glu249del	inframe_deletion	4/17	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

398

AN:

151762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00263

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00890

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00358

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.00248

AC:

608

AN:

244920

Hom.:

AF XY:

0.00243

AC XY:

322

AN XY:

132262

show subpopulations

Gnomad AFR exome

AF:

0.000379

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.000503

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000333

Gnomad FIN exome

AF:

0.00461

Gnomad NFE exome

AF:

0.00399

Gnomad OTH exome

AF:

0.00249

GnomAD4 exome

AF:

0.00292

AC:

4195

AN:

1437226

Hom.:

AF XY:

0.00289

AC XY:

2070

AN XY:

716052

show subpopulations

Gnomad4 AFR exome

AF:

0.000425

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.000501

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000351

Gnomad4 FIN exome

AF:

0.00547

Gnomad4 NFE exome

AF:

0.00337

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.00262

AC:

398

AN:

151884

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.00263

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00890

Gnomad4 NFE

AF:

0.00358

Gnomad4 OTH

AF:

0.000476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

YTHDC1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 25, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

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