Genetic Variant NM_001167740.2:c.813+8G>A (chr1-245915522-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167740.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMYD3	NM_001167740.2	MANE Select	c.813+8G>A	splice_region intron	N/A	NP_001161212.1	Q9H7B4-1
SMYD3	NM_001375962.1		c.702+12409G>A	intron	N/A	NP_001362891.1
SMYD3	NM_001375963.1		c.636+8G>A	splice_region intron	N/A	NP_001362892.1	Q9H7B4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMYD3	ENST00000490107.6	TSL:1 MANE Select	c.813+8G>A	splice_region intron	N/A	ENSP00000419184.2	Q9H7B4-1
SMYD3	ENST00000366516.5	TSL:1	n.1168+8G>A	splice_region intron	N/A
SMYD3	ENST00000366517.5	TSL:1	n.677+8G>A	splice_region intron	N/A

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

GnomAD2 exomes

AF:

0.00777

AC:

1949

AN:

250730

AF XY:

0.00649

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 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

African (AFR)

AF:

0.0676

AC:

2232

AN:

33030

American (AMR)

AF:

0.0101

AC:

452

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.0136

AC:

353

AN:

26026

East Asian (EAS)

AF:

0.00477

AC:

189

AN:

39610

South Asian (SAS)

AF:

0.000770

AC:

AN:

85724

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.0174

AC:

100

AN:

5732

European-Non Finnish (NFE)

AF:

0.00178

AC:

1952

AN:

1095494

Other (OTH)

AF:

0.0103

AC:

614

AN:

59710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

268

536

803

1071

1339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0220

AC:

3349

AN:

152240

Hom.:

108

Cov.:

AF XY:

0.0220

AC XY:

1636

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0675

AC:

2806

AN:

41544

American (AMR)

AF:

0.0166

AC:

254

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3472

East Asian (EAS)

AF:

0.00676

AC:

AN:

5178

South Asian (SAS)

AF:

0.00145

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00228

AC:

155

AN:

68032

Other (OTH)

AF:

0.0204

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

155

310

466

621

776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.00317

EpiControl

AF:

0.00422

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.5

(source)

DANN

Benign

0.47

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over