chr1-246096073-G-A

Position:

• chr1-246096073-G-A

Variant summary

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

The NM_001167740.2(SMYD3):​c.532-166136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,958 control chromosomes in the GnomAD database, including 12,707 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 0.36 (12707 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.532-166136C>T		intron_variant		ENST00000490107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.532-166136C>T		intron_variant		1	NM_001167740.2	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54476 AN: 151840 Hom.: 12680 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.359 AC: 54556 AN: 151958 Hom.: 12707 Cov.: 32 AF XY: 0.365 AC XY: 27118 AN XY: 74280

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.311

Alfa AF: 0.287 Hom.: 1037

Bravo AF: 0.378

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.52

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: rs2361364; hg19: chr1-246259375;