4-68337208-TTCC-T

Variant names:

• chr4-68337208-TTCC-T
• rs566379464
• NM_001031732.4:c.699_701delGGA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001031732.4(YTHDC1):​c.699_701delGGA​(p.Glu234del) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.16

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]

ACMG classification

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 rank	MANE	Protein	UniProt
YTHDC1	NM_001031732.4	c.699_701delGGA	p.Glu234del	disruptive_inframe_deletion	Exon 4 of 17	ENST00000344157.9	NP_001026902.1
YTHDC1	NM_001330698.2	c.699_701delGGA	p.Glu234del	disruptive_inframe_deletion	Exon 4 of 17		NP_001317627.1
YTHDC1	NM_133370.4	c.699_701delGGA	p.Glu234del	disruptive_inframe_deletion	Exon 4 of 16		NP_588611.2
YTHDC1	XM_005265708.4	c.699_701delGGA	p.Glu234del	disruptive_inframe_deletion	Exon 4 of 16		XP_005265765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YTHDC1	ENST00000344157.9	c.699_701delGGA	p.Glu234del	disruptive_inframe_deletion	Exon 4 of 17	1	NM_001031732.4	ENSP00000339245.4
YTHDC1	ENST00000355665.7	c.699_701delGGA	p.Glu234del	disruptive_inframe_deletion	Exon 4 of 16	1		ENSP00000347888.3
YTHDC1	ENST00000579690.5	c.699_701delGGA	p.Glu234del	disruptive_inframe_deletion	Exon 4 of 17	5		ENSP00000463982.1

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 398 AN: 151762 Hom.: 2 Cov.: 32

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.: 3 AF XY: 0.00243 AC XY: 322 AN XY: 132262

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.: 9 AF XY: 0.00289 AC XY: 2070 AN XY: 716052

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.: 2 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74228

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: no assertion criteria provided

Submissions by phenotype

YTHDC1-related disorder Benign:1

Apr 25, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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

Other links and lift over

dbSNP: rs566379464; hg19: chr4-69202926;