Variant chr1-245915522-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001167740.2(SMYD3):c.813+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,595,584 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 108 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 108 hom. )

Consequence

SMYD3
NM_001167740.2 splice_region, intron

Scores

Splicing: ADA: 0.0007896

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.468

Variant links:

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]

SMYD3 links:

SMYD3 (HGNC:):

SMYD3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-245915522-C-T is Benign according to our data. Variant chr1-245915522-C-T is described in ClinVar as [Benign]. Clinvar id is 778257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD3	NM_001167740.2 linkuse as main transcript	c.813+8G>A		splice_region_variant, intron_variant		ENST00000490107.6	NP_001161212.1	Q9H7B4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6 linkuse as main transcript	c.813+8G>A		splice_region_variant, intron_variant		1	NM_001167740.2	ENSP00000419184.2		Q9H7B4-1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3335

AN:

152122

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0674

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00674

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00777

AC:

1949

AN:

250730

Hom.:

AF XY:

0.00649

AC XY:

880

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.0653

Gnomad AMR exome

AF:

0.00935

Gnomad ASJ exome

AF:

0.0143

Gnomad EAS exome

AF:

0.00550

Gnomad SAS exome

AF:

0.000721

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00413

AC:

5959

AN:

1443344

Hom.:

108

Cov.:

AF XY:

0.00391

AC XY:

2816

AN XY:

719402

show subpopulations

Gnomad4 AFR exome

AF:

0.0676

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.00477

Gnomad4 SAS exome

AF:

0.000770

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.0220

AC:

3349

AN:

152240

Hom.:

108

Cov.:

AF XY:

0.0220

AC XY:

1636

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0675

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00676

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.00317

EpiControl

AF:

0.00422

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.5

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00079

dbscSNV1_RF

Benign

0.016

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over