chr1-245750982-G-A

Variant names:

• chr1-245750982-G-A
• rs2362932
• NM_001167740.2:c.1186-1318C>T

Variant summary

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

The NM_001167740.2(SMYD3):​c.1186-1318C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,050 control chromosomes in the GnomAD database, including 9,185 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 0.34 (9185 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD3	NM_001167740.2	MANE Select	c.1186-1318C>T		intron	N/A	NP_001161212.1
	SMYD3	NM_001375962.1		c.1075-1318C>T		intron	N/A	NP_001362891.1
	SMYD3	NM_001375963.1		c.1009-1318C>T		intron	N/A	NP_001362892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD3	ENST00000490107.6	TSL:1 MANE Select	c.1186-1318C>T		intron	N/A	ENSP00000419184.2
	SMYD3	ENST00000366516.5	TSL:1	n.1541-1318C>T		intron	N/A
	SMYD3	ENST00000366517.5	TSL:1	n.1050-1318C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51779 AN: 151932 Hom.: 9183 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.341 AC: 51822 AN: 152050 Hom.: 9185 Cov.: 32 AF XY: 0.347 AC XY: 25808 AN XY: 74338

African (AFR) AF: 0.415 AC: 17197 AN: 41472

American (AMR) AF: 0.337 AC: 5155 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1181 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2868 AN: 5164

South Asian (SAS) AF: 0.417 AC: 2009 AN: 4814

European-Finnish (FIN) AF: 0.368 AC: 3885 AN: 10554

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18477 AN: 67970

Other (OTH) AF: 0.330 AC: 696 AN: 2112

Alfa AF: 0.296 Hom.: 27586

Bravo AF: 0.341

Asia WGS AF: 0.500 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.8
DANN	Benign	0.56
PhyloP100		0.48
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: rs2362932; hg19: chr1-245914284;