NM_001167740.2:c.532-189024G>A

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167740.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD3	NM_001167740.2	MANE Select	c.532-189024G>A		intron	N/A	NP_001161212.1	Q9H7B4-1
	SMYD3	NM_001375962.1		c.532-189024G>A		intron	N/A	NP_001362891.1
	SMYD3	NM_001375963.1		c.355-189024G>A		intron	N/A	NP_001362892.1	Q9H7B4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD3	ENST00000490107.6	TSL:1 MANE Select	c.532-189024G>A		intron	N/A	ENSP00000419184.2	Q9H7B4-1
	SMYD3	ENST00000630181.2	TSL:2	c.355-189024G>A		intron	N/A	ENSP00000487434.1	Q9H7B4-3
	SMYD3	ENST00000391836.3	TSL:5	c.-37+67782G>A		intron	N/A	ENSP00000375712.2	A8MXR1

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 v4.9

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;