rs12780826

Positions:

• chr10-18655968-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351116.2(NSUN6):​c.-112-793A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,254 control chromosomes in the GnomAD database, including 1,302 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 0.11 (1302 hom., cov: 32)
• Consequence: NSUN6 NM_001351116.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

Genes affected

NSUN6 (HGNC:23529): (NOP2/Sun RNA methyltransferase 6) Enables tRNA (cytosine-5-)-methyltransferase activity and tRNA binding activity. Involved in tRNA C5-cytosine methylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSUN6	NM_001351116.2	c.-112-793A>T		intron_variant			NP_001338045.1
NSUN6	XM_011519384.2	c.-112-793A>T		intron_variant			XP_011517686.1
NSUN6	XM_011519385.2	c.-112-793A>T		intron_variant			XP_011517687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSUN6	ENST00000607346.1	c.-112-793A>T		intron_variant, NMD_transcript_variant		4		ENSP00000486203
NSUN6	ENST00000414939.1	n.326-793A>T		intron_variant, non_coding_transcript_variant		3
NSUN6	ENST00000444660.1	n.37-793A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16958 AN: 152136 Hom.: 1297 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.0835

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.111 AC: 16969 AN: 152254 Hom.: 1302 Cov.: 32 AF XY: 0.114 AC XY: 8450 AN XY: 74424

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.0833

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.104

Alfa AF: 0.137 Hom.: 213

Bravo AF: 0.107

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12780826; hg19: chr10-18944897;