rs4654092

Positions:

• chr1-246156180-A-G
• chr1-246156180-A-T

Variant summary

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

The NM_001167740.2(SMYD3):​c.531+171021T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,918 control chromosomes in the GnomAD database, including 24,986 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 0.52 (24986 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813

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]

SMYD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.531+171021T>C		intron_variant		ENST00000490107.6	NP_001161212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.531+171021T>C		intron_variant		1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78745 AN: 151798 Hom.: 24988 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.518 AC: 78750 AN: 151918 Hom.: 24986 Cov.: 31 AF XY: 0.507 AC XY: 37616 AN XY: 74264

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.0547

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.554

Alfa AF: 0.653 Hom.: 22581

Bravo AF: 0.496

Asia WGS AF: 0.213 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.60

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: rs4654092; hg19: chr1-246319482;