1-245998954-C-A

Position:

• chr1-245998954-C-A

Variant summary

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

The NM_001167740.2(SMYD3):​c.532-69017G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,096 control chromosomes in the GnomAD database, including 953 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 0.10 (953 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.532-69017G>T		intron_variant		ENST00000490107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.532-69017G>T		intron_variant		1	NM_001167740.2	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15406 AN: 151978 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.101 AC: 15418 AN: 152096 Hom.: 953 Cov.: 32 AF XY: 0.106 AC XY: 7865 AN XY: 74338

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0825 Hom.: 145

Bravo AF: 0.0986

Asia WGS AF: 0.143 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0090
DANN	Benign	0.72

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: rs2105158; hg19: chr1-246162256;