rs751003108

Variant names:

• chr4-68314262-C-A
• NM_001031732.4:c.2021G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-68314262-C-A
• chr4-68314262-C-G
• chr4-68314262-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031732.4(YTHDC1):​c.2021G>T​(p.Arg674Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,842 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: 6.8e-7 (0 hom.)
• Consequence: YTHDC1 NM_001031732.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.10

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3863826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YTHDC1	NM_001031732.4	c.2021G>T	p.Arg674Leu	missense_variant	Exon 17 of 17	ENST00000344157.9	NP_001026902.1
YTHDC1	NM_001330698.2	c.2045G>T	p.Arg682Leu	missense_variant	Exon 17 of 17		NP_001317627.1
YTHDC1	NM_133370.4	c.1967G>T	p.Arg656Leu	missense_variant	Exon 16 of 16		NP_588611.2
YTHDC1	XM_005265708.4	c.1991G>T	p.Arg664Leu	missense_variant	Exon 16 of 16		XP_005265765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YTHDC1	ENST00000344157.9	c.2021G>T	p.Arg674Leu	missense_variant	Exon 17 of 17	1	NM_001031732.4	ENSP00000339245.4
YTHDC1	ENST00000355665.7	c.1967G>T	p.Arg656Leu	missense_variant	Exon 16 of 16	1		ENSP00000347888.3
YTHDC1	ENST00000579690.5	c.2045G>T	p.Arg682Leu	missense_variant	Exon 17 of 17	5		ENSP00000463982.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	0.0073	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;.;.
Eigen	Benign	-0.035
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.3	N;N;.
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D;D;.
Sift4G	Benign	0.10	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.68
MutPred		0.25		Loss of sheet (P = 0.0104);.;.;
MVP		0.068
MPC		0.74
ClinPred		0.91	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69179980;