1-246118961-C-T

Variant names:

• chr1-246118961-C-T
• rs12404212
• NM_001167740.2:c.532-189024G>A

Variant summary

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

The NM_001167740.2(SMYD3):​c.532-189024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 151,974 control chromosomes in the GnomAD database, including 2,120 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 0.14 (2120 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.532-189024G>A		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.532-189024G>A		intron_variant	Intron 5 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21982 AN: 151856 Hom.: 2115 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.145 AC: 22029 AN: 151974 Hom.: 2120 Cov.: 31 AF XY: 0.145 AC XY: 10778 AN XY: 74286

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0830 Hom.: 638

Bravo AF: 0.140

Asia WGS AF: 0.192 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.066
DANN	Benign	0.51

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: rs12404212; hg19: chr1-246282263;