chr1-245927813-C-G

Position:

• chr1-245927813-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.702+118G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 717,602 control chromosomes in the GnomAD database, including 265,051 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 0.83 (53533 hom., cov: 31)
  • Exomes 𝑓: 0.86 (211518 hom.)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.702+118G>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.702+118G>C		intron_variant		1	NM_001167740.2	ENSP00000419184	P1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126663 AN: 151974 Hom.: 53508 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.832

GnomAD4 exome AF: 0.859 AC: 485548 AN: 565510 Hom.: 211518 AF XY: 0.856 AC XY: 260110 AN XY: 303884

Gnomad4 AFR exome AF: 0.735

Gnomad4 AMR exome AF: 0.869

Gnomad4 ASJ exome AF: 0.897

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.801

Gnomad4 FIN exome AF: 0.866

Gnomad4 NFE exome AF: 0.903

Gnomad4 OTH exome AF: 0.854

GnomAD4 genome AF: 0.833 AC: 126732 AN: 152092 Hom.: 53533 Cov.: 31 AF XY: 0.831 AC XY: 61745 AN XY: 74342

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.828

Alfa AF: 0.865 Hom.: 7095

Bravo AF: 0.828

Asia WGS AF: 0.641 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.020
DANN	Benign	0.36

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: rs2275313; hg19: chr1-246091115;