chr4-68314134-T-C

Variant names:

• chr4-68314134-T-C
• NM_001031732.4:c.2149A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031732.4(YTHDC1):​c.2149A>G​(p.Arg717Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YTHDC1 NM_001031732.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14550582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YTHDC1	NM_001031732.4	c.2149A>G	p.Arg717Gly	missense_variant	Exon 17 of 17	ENST00000344157.9	NP_001026902.1
YTHDC1	NM_001330698.2	c.2173A>G	p.Arg725Gly	missense_variant	Exon 17 of 17		NP_001317627.1
YTHDC1	NM_133370.4	c.2095A>G	p.Arg699Gly	missense_variant	Exon 16 of 16		NP_588611.2
YTHDC1	XM_005265708.4	c.2119A>G	p.Arg707Gly	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.2149A>G	p.Arg717Gly	missense_variant	Exon 17 of 17	1	NM_001031732.4	ENSP00000339245.4
YTHDC1	ENST00000355665.7	c.2095A>G	p.Arg699Gly	missense_variant	Exon 16 of 16	1		ENSP00000347888.3
YTHDC1	ENST00000579690.5	c.2173A>G	p.Arg725Gly	missense_variant	Exon 17 of 17	5		ENSP00000463982.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2149A>G (p.R717G) alteration is located in exon 17 (coding exon 17) of the YTHDC1 gene. This alteration results from a A to G substitution at nucleotide position 2149, causing the arginine (R) at amino acid position 717 to be replaced by a glycine (G). 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.12	N;N;.
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D;.
Sift4G	Uncertain	0.041	D;D;D
Polyphen		0.90	P;P;.
Vest4		0.14
MutPred		0.33		Gain of relative solvent accessibility (P = 0.0166);.;.;
MVP		0.043
MPC		0.77
ClinPred		0.59	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.11

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: chr4-69179852;