rs2791398

chr1-245802249-A-Gchr1-245802249-A-T

Variant summary

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

The NM_001167740.2(SMYD3):c.1077-38100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,196 control chromosomes in the GnomAD database, including 60,574 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 0.89 (60574 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.1077-38100T>C		intron_variant		ENST00000490107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.1077-38100T>C		intron_variant		1	NM_001167740.2	P1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135322 AN: 152078 Hom.: 60517 Cov.: 31

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.890 AC: 135435 AN: 152196 Hom.: 60574 Cov.: 31 AF XY: 0.885 AC XY: 65804 AN XY: 74388

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.889

Alfa AF: 0.877 Hom.: 79524

Bravo AF: 0.895

Asia WGS AF: 0.916 AC: 3184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.26
Dann	Benign	0.40

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: rs2791398; hg19: chr1-245965551;