rs113636517

Variant names:

• chr2-88087989-C-A
• rs113636517
• NM_198274.4:c.442C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-88087989-C-A
• chr2-88087989-C-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.82
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 AC in GnomAd4 at 471 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198274.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD1	NM_198274.4	MANE Select	c.442C>A	p.Arg148Arg	synonymous	Exon 3 of 10	NP_938015.1	Q8NB12
	SMYD1	NM_001330364.2		c.442C>A	p.Arg148Arg	synonymous	Exon 3 of 9	NP_001317293.1	E9PHG3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD1	ENST00000419482.7	TSL:1 MANE Select	c.442C>A	p.Arg148Arg	synonymous	Exon 3 of 10	ENSP00000393453.2	Q8NB12
	SMYD1	ENST00000965777.1		c.442C>A	p.Arg148Arg	synonymous	Exon 3 of 11	ENSP00000635836.1
	SMYD1	ENST00000965776.1		c.538C>A	p.Arg180Arg	synonymous	Exon 4 of 11	ENSP00000635835.1

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 471 AN: 152190 Hom.: 2 Cov.: 32

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

GnomAD2 exomes AF: 0.00337 AC: 847 AN: 251328 AF XY: 0.00345

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 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.: 39 Cov.: 33 AF XY: 0.00582 AC XY: 4232 AN XY: 727232

African (AFR) AF: 0.000986 AC: 33 AN: 33480

American (AMR) AF: 0.000939 AC: 42 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00259 AC: 223 AN: 86258

European-Finnish (FIN) AF: 0.00256 AC: 137 AN: 53416

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.00718 AC: 7982 AN: 1112000

Other (OTH) AF: 0.00540 AC: 326 AN: 60390

GnomAD4 genome AF: 0.00309 AC: 471 AN: 152308 Hom.: 2 Cov.: 32 AF XY: 0.00266 AC XY: 198 AN XY: 74484

African (AFR) AF: 0.000962 AC: 40 AN: 41574

American (AMR) AF: 0.000457 AC: 7 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4828

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00556 AC: 378 AN: 68022

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.00303 Hom.: 1

Bravo AF: 0.00320

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00599

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs113636517; hg19: chr2-88387508; COSMIC: COSV101352562;