rs12066580

chr1-245840547-C-Achr1-245840547-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.1076+17949G>T		intron_variant		ENST00000490107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.1076+17949G>T		intron_variant		1	NM_001167740.2	P1

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

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.582

Alfa AF: 0.518 Hom.: 2497

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

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

LitVar

Other links and lift over

dbSNP: rs12066580; hg19: chr1-246003849;