rs12084862

Variant names:

• chr1-246039912-G-A
• rs12084862
• NM_001167740.2:c.532-109975C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-246039912-G-A
• chr1-246039912-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.85).
• 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 rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.532-109975C>T		intron_variant	Intron 5 of 11	ENST00000490107.6	NP_001161212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.532-109975C>T		intron_variant	Intron 5 of 11	1	NM_001167740.2	ENSP00000419184.2

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

African (AFR) AF: 0.610 AC: 25286 AN: 41446

American (AMR) AF: 0.371 AC: 5664 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3466

East Asian (EAS) AF: 0.824 AC: 4256 AN: 5166

South Asian (SAS) AF: 0.486 AC: 2341 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3842 AN: 10546

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16914 AN: 67980

Other (OTH) AF: 0.357 AC: 753 AN: 2112

Alfa AF: 0.310 Hom.: 26324

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
PhyloP100		-0.24
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: rs12084862; hg19: chr1-246203214;