rs12084862

chr1-246039912-G-Achr1-246039912-G-C

Variant summary

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

The NM_001167740.2(SMYD3):c.532-109975C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,012 control chromosomes in the GnomAD database, including 14,410 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 0.40 (14410 hom., cov: 33)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.532-109975C>T		intron_variant		ENST00000490107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.532-109975C>T		intron_variant		1	NM_001167740.2	P1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60433 AN: 151894 Hom.: 14375 Cov.: 33

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.398 AC: 60524 AN: 152012 Hom.: 14410 Cov.: 33 AF XY: 0.406 AC XY: 30186 AN XY: 74306

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.357

Alfa AF: 0.289 Hom.: 9887

Bravo AF: 0.411

Asia WGS AF: 0.647 AC: 2246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.5
Dann	Benign	0.59

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: rs12084862; hg19: chr1-246203214;