1-246209578-G-C

Position:

• chr1-246209578-G-C

Variant summary

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

The NM_001167740.2(SMYD3):​c.531+117623C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 142,612 control chromosomes in the GnomAD database, including 4,990 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 0.24 (4990 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.531+117623C>G		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+117623C>G		intron_variant		1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 33804 AN: 142512 Hom.: 4953 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.238 AC: 33885 AN: 142612 Hom.: 4990 Cov.: 32 AF XY: 0.242 AC XY: 16794 AN XY: 69500

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0816

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.182

Alfa AF: 0.0725 Hom.: 89

Bravo AF: 0.225

Asia WGS AF: 0.346 AC: 1199 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.66

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: rs10802346; hg19: chr1-246372880;