chr4-68337217-C-T

Variant names:

• chr4-68337217-C-T
• rs780031117
• NM_001031732.4:c.693G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001031732.4(YTHDC1):​c.693G>A​(p.Glu231Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: YTHDC1 NM_001031732.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.947
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.947 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YTHDC1	NM_001031732.4	MANE Select	c.693G>A	p.Glu231Glu	synonymous	Exon 4 of 17	NP_001026902.1	Q96MU7-1
	YTHDC1	NM_001330698.2		c.693G>A	p.Glu231Glu	synonymous	Exon 4 of 17	NP_001317627.1	J3QR07
	YTHDC1	NM_133370.4		c.693G>A	p.Glu231Glu	synonymous	Exon 4 of 16	NP_588611.2	Q96MU7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YTHDC1	ENST00000344157.9	TSL:1 MANE Select	c.693G>A	p.Glu231Glu	synonymous	Exon 4 of 17	ENSP00000339245.4	Q96MU7-1
	YTHDC1	ENST00000355665.7	TSL:1	c.693G>A	p.Glu231Glu	synonymous	Exon 4 of 16	ENSP00000347888.3	Q96MU7-2
	YTHDC1	ENST00000936188.1		c.693G>A	p.Glu231Glu	synonymous	Exon 4 of 18	ENSP00000606247.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447326 Hom.: 0 Cov.: 29 AF XY: 0.00000278 AC XY: 2 AN XY: 720504

African (AFR) AF: 0.00 AC: 0 AN: 33140

American (AMR) AF: 0.00 AC: 0 AN: 44300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.00 AC: 0 AN: 85716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1099784

Other (OTH) AF: 0.00 AC: 0 AN: 59890

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.8
DANN	Benign	0.30
PhyloP100		0.95

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

Other links and lift over

dbSNP: rs780031117; hg19: chr4-69202935; COSMIC: COSV60010469; COSMIC: COSV60010469;