10-18550421-A-G

Variant names:

• chr10-18550421-A-G
• rs6482516
• NM_182543.5:c.1071+1402T>C

Variant summary

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

The NM_182543.5(NSUN6):​c.1071+1402T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,098 control chromosomes in the GnomAD database, including 40,867 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 0.73 (40867 hom., cov: 32)
• Consequence: NSUN6 NM_182543.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSUN6	NM_182543.5	c.1071+1402T>C		intron_variant	Intron 9 of 10	ENST00000377304.7	NP_872349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSUN6	ENST00000377304.7	c.1071+1402T>C		intron_variant	Intron 9 of 10	1	NM_182543.5	ENSP00000366519.4
NSUN6	ENST00000493816.1	n.105+1297T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111102 AN: 151980 Hom.: 40855 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.731 AC: 111151 AN: 152098 Hom.: 40867 Cov.: 32 AF XY: 0.732 AC XY: 54397 AN XY: 74356

African (AFR) AF: 0.671 AC: 27830 AN: 41470

American (AMR) AF: 0.724 AC: 11055 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2395 AN: 3470

East Asian (EAS) AF: 0.968 AC: 5002 AN: 5170

South Asian (SAS) AF: 0.767 AC: 3696 AN: 4820

European-Finnish (FIN) AF: 0.765 AC: 8098 AN: 10586

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50666 AN: 68000

Other (OTH) AF: 0.718 AC: 1517 AN: 2114

Alfa AF: 0.734 Hom.: 18309

Bravo AF: 0.722

Asia WGS AF: 0.820 AC: 2849 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		0.13
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: rs6482516; hg19: chr10-18839350;