1-246460741-G-C

Position:

• chr1-246460741-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001167740.2(SMYD3):​c.164+46313C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,092 control chromosomes in the GnomAD database, including 13,242 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 0.39 (13242 hom., cov: 33)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.164+46313C>G		intron_variant		ENST00000490107.6
SMYD3	NM_001375962.1	c.164+46313C>G		intron_variant
SMYD3	XM_047428020.1	c.-14+20444C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.164+46313C>G		intron_variant		1	NM_001167740.2	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59444 AN: 151974 Hom.: 13231 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.391 AC: 59455 AN: 152092 Hom.: 13242 Cov.: 33 AF XY: 0.400 AC XY: 29727 AN XY: 74358

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.405

Alfa AF: 0.286 Hom.: 821

Bravo AF: 0.383

Asia WGS AF: 0.537 AC: 1869 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.82

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: rs946001; hg19: chr1-246624043;