rs16930253

Variant names:

• chr8-63201708-G-T
• rs16930253
• NM_152758.6:c.1735-7975G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152758.6(YTHDF3):​c.1735-7975G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,184 control chromosomes in the GnomAD database, including 841 homozygotes. 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: 𝑓 0.099 (841 hom., cov: 32)
• Consequence: YTHDF3 NM_152758.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 1 publications found

Genes affected

YTHDF3 (HGNC:26465): (YTH N6-methyladenosine RNA binding protein F3) This gene encodes a member of the YTH (YT521-B homology) domain protein family. The YTH domain is common in eukaryotes, is often found in the middle of the protein sequence, and may function in binding to RNA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152758.6. 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
	YTHDF3	NM_152758.6	MANE Select	c.1735-7975G>T		intron	N/A	NP_689971.4
	YTHDF3	NM_001277813.2		c.1744-7975G>T		intron	N/A	NP_001264742.1	A0A087WY31
	YTHDF3	NM_001277814.2		c.1744-7975G>T		intron	N/A	NP_001264743.1	A0A087WY31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YTHDF3	ENST00000539294.6	TSL:1 MANE Select	c.1735-7975G>T		intron	N/A	ENSP00000473496.2	Q7Z739
	YTHDF3	ENST00000623280.3	TSL:1	c.1582-7975G>T		intron	N/A	ENSP00000485046.1	A0A024R7W5
	YTHDF3	ENST00000615676.1	TSL:1	n.*1640-7975G>T		intron	N/A	ENSP00000483267.1	A0A087X0C3

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14985 AN: 152066 Hom.: 839 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0999

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0986 AC: 15005 AN: 152184 Hom.: 841 Cov.: 32 AF XY: 0.100 AC XY: 7465 AN XY: 74416

African (AFR) AF: 0.113 AC: 4679 AN: 41512

American (AMR) AF: 0.0992 AC: 1516 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1176 AN: 5186

South Asian (SAS) AF: 0.105 AC: 509 AN: 4826

European-Finnish (FIN) AF: 0.100 AC: 1064 AN: 10592

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0808 AC: 5497 AN: 68002

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.0874 Hom.: 121

Bravo AF: 0.0955

Asia WGS AF: 0.174 AC: 604 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs16930253; hg19: chr8-64114266;