rs4654180

chr1-245985489-C-Achr1-245985489-C-G

Variant summary

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

The NM_001167740.2(SMYD3):c.532-55552G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,120 control chromosomes in the GnomAD database, including 1,012 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 0.11 (1012 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.532-55552G>T		intron_variant		ENST00000490107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.532-55552G>T		intron_variant		1	NM_001167740.2	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16682 AN: 152002 Hom.: 1007 Cov.: 31

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.110 AC: 16693 AN: 152120 Hom.: 1012 Cov.: 31 AF XY: 0.114 AC XY: 8474 AN XY: 74388

Gnomad4 AFR AF: 0.0670

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.116

Alfa AF: 0.113 Hom.: 1447

Bravo AF: 0.109

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.75

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: rs4654180; hg19: chr1-246148791;