rs6426327

Positions:

• chr1-245926509-G-A
• chr1-245926509-G-C

Variant summary

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

The NM_001167740.2(SMYD3):​c.702+1422C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,088 control chromosomes in the GnomAD database, including 41,078 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 0.69 (41078 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD3	NM_001167740.2	c.702+1422C>T		intron_variant		ENST00000490107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD3	ENST00000490107.6	c.702+1422C>T		intron_variant		1	NM_001167740.2	P1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104732 AN: 151970 Hom.: 41077 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.689 AC: 104748 AN: 152088 Hom.: 41078 Cov.: 32 AF XY: 0.688 AC XY: 51184 AN XY: 74356

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.720

Alfa AF: 0.846 Hom.: 70120

Bravo AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.37

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: rs6426327; hg19: chr1-246089811; COSMIC: COSV100830617; COSMIC: COSV100830617;