rs12066580

Variant names:

• chr1-245840547-C-A
• rs12066580
• NM_001167740.2:c.1076+17949G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-245840547-C-A
• chr1-245840547-C-T

Variant summary

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

The NM_001167740.2(SMYD3):​c.1076+17949G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,794 control chromosomes in the GnomAD database, including 24,732 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 0.54 (24732 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 1 publications found

Genes affected

SMYD3 (HGNC:15513): (SET and MYND domain containing 3) This gene encodes a histone methyltransferase which functions in RNA polymerase II complexes by an interaction with a specific RNA helicase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.1076+17949G>T		intron_variant	Intron 10 of 11	ENST00000490107.6	NP_001161212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.1076+17949G>T		intron_variant	Intron 10 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 81992 AN: 151676 Hom.: 24745 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.540 AC: 81982 AN: 151794 Hom.: 24732 Cov.: 31 AF XY: 0.534 AC XY: 39588 AN XY: 74164

African (AFR) AF: 0.321 AC: 13262 AN: 41352

American (AMR) AF: 0.533 AC: 8126 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2258 AN: 3466

East Asian (EAS) AF: 0.135 AC: 698 AN: 5176

South Asian (SAS) AF: 0.362 AC: 1737 AN: 4802

European-Finnish (FIN) AF: 0.649 AC: 6828 AN: 10526

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 46969 AN: 67922

Other (OTH) AF: 0.582 AC: 1227 AN: 2108

Alfa AF: 0.545 Hom.: 6839

Bravo AF: 0.523

Asia WGS AF: 0.272 AC: 946 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.7
DANN	Benign	0.58
PhyloP100		0.036
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: rs12066580; hg19: chr1-246003849;