1-246118961-C-T

Variant names:

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

Variant summary

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

The NM_001167740.2(SMYD3):​c.532-189024G>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
• Publications: 3 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=-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

African (AFR) AF: 0.267 AC: 11071 AN: 41410

American (AMR) AF: 0.0612 AC: 935 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3470

East Asian (EAS) AF: 0.156 AC: 808 AN: 5174

South Asian (SAS) AF: 0.197 AC: 950 AN: 4812

European-Finnish (FIN) AF: 0.152 AC: 1600 AN: 10548

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6058 AN: 67974

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.0909 Hom.: 1013

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
PhyloP100		-1.1
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: rs12404212; hg19: chr1-246282263;