Variant 4-68318841-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001031732.4(YTHDC1):c.1706A>G(p.Tyr569Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

YTHDC1
NM_001031732.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.67

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 Uncertain_significance. 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YTHDC1	NM_001031732.4 linkuse as main transcript	c.1706A>G	p.Tyr569Cys	missense_variant	13/17	ENST00000344157.9	NP_001026902.1	Q96MU7-1
YTHDC1	NM_001330698.2 linkuse as main transcript	c.1706A>G	p.Tyr569Cys	missense_variant	13/17		NP_001317627.1	Q96MU7J3QR07
YTHDC1	NM_133370.4 linkuse as main transcript	c.1652A>G	p.Tyr551Cys	missense_variant	12/16		NP_588611.2	Q96MU7-2
YTHDC1	XM_005265708.4 linkuse as main transcript	c.1652A>G	p.Tyr551Cys	missense_variant	12/16		XP_005265765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
YTHDC1	ENST00000344157.9 linkuse as main transcript	c.1706A>G	p.Tyr569Cys	missense_variant	13/17	1	NM_001031732.4	ENSP00000339245.4	Q96MU7-1
YTHDC1	ENST00000355665.7 linkuse as main transcript	c.1652A>G	p.Tyr551Cys	missense_variant	12/16	1		ENSP00000347888.3	Q96MU7-2
YTHDC1	ENST00000579690.5 linkuse as main transcript	c.1706A>G	p.Tyr569Cys	missense_variant	13/17	5		ENSP00000463982.1	J3QR07

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251184

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.1706A>G (p.Y569C) alteration is located in exon 13 (coding exon 13) of the YTHDC1 gene. This alteration results from a A to G substitution at nucleotide position 1706, causing the tyrosine (Y) at amino acid position 569 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.8

D;D;.

REVEL

Benign

0.22

Sift

Uncertain

0.0060

D;D;.

Sift4G

Benign

0.14

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.68

MutPred

0.27

Loss of phosphorylation at Y569 (P = 0.0059);.;Loss of phosphorylation at Y569 (P = 0.0059);

MVP

0.18

MPC

1.5

ClinPred

0.86

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.18

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