2-88067959-T-A

Variant names:

• chr2-88067959-T-A
• rs143754722
• NM_198274.4:c.95T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198274.4(SMYD1):​c.95T>A​(p.Ile32Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I32T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMYD1 NM_198274.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56
• Publications: 2 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41714248).

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.95T>A	p.Ile32Asn	missense	Exon 1 of 10	NP_938015.1	Q8NB12
	SMYD1	NM_001330364.2		c.95T>A	p.Ile32Asn	missense	Exon 1 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.95T>A	p.Ile32Asn	missense	Exon 1 of 10	ENSP00000393453.2	Q8NB12
	SMYD1	ENST00000965777.1		c.95T>A	p.Ile32Asn	missense	Exon 1 of 11	ENSP00000635836.1
	SMYD1	ENST00000965776.1		c.95T>A	p.Ile32Asn	missense	Exon 1 of 11	ENSP00000635835.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.34	N
PhyloP100		5.6
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.78	P
Vest4		0.46
MutPred		0.46		Gain of sheet (P = 0.039)
MVP		0.88
MPC		0.30
ClinPred		0.91	D
GERP RS		4.7
PromoterAI		-0.037	Neutral
Varity_R		0.64
gMVP		0.78
Mutation Taster		=49/51	disease causing

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: rs143754722; hg19: chr2-88367478;