1-245830733-G-T

Position:

• chr1-245830733-G-T

Variant summary

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

The NM_001167740.2(SMYD3):​c.1076+27763C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,134 control chromosomes in the GnomAD database, including 51,402 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 0.80 (51402 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.1076+27763C>A		intron_variant		ENST00000490107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.1076+27763C>A		intron_variant		1	NM_001167740.2	P1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122026 AN: 152016 Hom.: 51381 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.803 AC: 122089 AN: 152134 Hom.: 51402 Cov.: 32 AF XY: 0.802 AC XY: 59676 AN XY: 74388

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.958

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.829

Alfa AF: 0.911 Hom.: 56612

Bravo AF: 0.771

Asia WGS AF: 0.745 AC: 2593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.86
DANN	Benign	0.68

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: rs7514038; hg19: chr1-245994035;