Variant 2-88087989-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_198274.4(SMYD1):c.442C>A(p.Arg148Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 1,614,178 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 39 hom. )

Consequence

SMYD1
NM_198274.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.82

Variant links:

Genes affected

SMYD1 (HGNC:20986): (SET and MYND domain containing 1) Predicted to enable histone-lysine N-methyltransferase activity. Involved in positive regulation of myoblast differentiation and positive regulation of myotube differentiation. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SMYD1 links:

SMYD1 (HGNC:):

SMYD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 2-88087989-C-A is Benign according to our data. Variant chr2-88087989-C-A is described in ClinVar as [Benign]. Clinvar id is 781946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.82 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD1	NM_198274.4 linkuse as main transcript	c.442C>A	p.Arg148Arg	synonymous_variant	3/10	ENST00000419482.7	NP_938015.1	Q8NB12Q5HYE8
SMYD1	NM_001330364.2 linkuse as main transcript	c.442C>A	p.Arg148Arg	synonymous_variant	3/9		NP_001317293.1	E9PHG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMYD1	ENST00000419482.7 linkuse as main transcript	c.442C>A	p.Arg148Arg	synonymous_variant	3/10	1	NM_198274.4	ENSP00000393453.2	Q8NB12
SMYD1	ENST00000444564.2 linkuse as main transcript	c.442C>A	p.Arg148Arg	synonymous_variant	3/9	5		ENSP00000407888.2	E9PHG3
SMYD1	ENST00000438570.1 linkuse as main transcript	c.294+3517C>A		intron_variant		2		ENSP00000387482.1	C9JUP3
SMYD1	ENST00000468008.1 linkuse as main transcript	n.472C>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

471

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00556

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00337

AC:

847

AN:

251328

Hom.:

AF XY:

0.00345

AC XY:

468

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.00546

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00601

AC:

8783

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

4232

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.00256

Gnomad4 NFE exome

AF:

0.00718

Gnomad4 OTH exome

AF:

0.00540

GnomAD4 genome

AF:

0.00309

AC:

471

AN:

152308

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00556

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00328

Hom.:

Bravo

AF:

0.00320

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00599

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 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.91

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

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