rs4654179

Variant names:

• chr1-245981134-C-T
• rs4654179
• NM_001167740.2:c.532-51197G>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.532-51197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 152,184 control chromosomes in the GnomAD database, including 881 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 0.096 (881 hom., cov: 33)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.532-51197G>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.532-51197G>A		intron_variant	Intron 5 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14624 AN: 152068 Hom.: 878 Cov.: 33

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0991

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0962 AC: 14636 AN: 152184 Hom.: 881 Cov.: 33 AF XY: 0.101 AC XY: 7478 AN XY: 74404

African (AFR) AF: 0.0330 AC: 1371 AN: 41516

American (AMR) AF: 0.152 AC: 2329 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3472

East Asian (EAS) AF: 0.0991 AC: 514 AN: 5186

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4822

European-Finnish (FIN) AF: 0.112 AC: 1181 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7492 AN: 68004

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.116 Hom.: 206

Bravo AF: 0.0930

Asia WGS AF: 0.133 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.55
DANN	Benign	0.43
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: rs4654179; hg19: chr1-246144436;