2-88084392-C-T

Position:

• chr2-88084392-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198274.4(SMYD1):​c.214C>T​(p.His72Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMYD1 NM_198274.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26946026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD1	NM_198274.4	c.214C>T	p.His72Tyr	missense_variant	2/10	ENST00000419482.7	NP_938015.1
SMYD1	NM_001330364.2	c.214C>T	p.His72Tyr	missense_variant	2/9		NP_001317293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD1	ENST00000419482.7	c.214C>T	p.His72Tyr	missense_variant	2/10	1	NM_198274.4	ENSP00000393453.2
SMYD1	ENST00000444564.2	c.214C>T	p.His72Tyr	missense_variant	2/9	5		ENSP00000407888.2
SMYD1	ENST00000438570.1	c.214C>T	p.His72Tyr	missense_variant	2/3	2		ENSP00000387482.1
SMYD1	ENST00000468008.1	n.244C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.214C>T (p.H72Y) alteration is located in exon 2 (coding exon 2) of the SMYD1 gene. This alteration results from a C to T substitution at nucleotide position 214, causing the histidine (H) at amino acid position 72 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.095	N;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.081	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0040	B;.;B
Vest4		0.33
MutPred		0.54		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.29
MPC		0.087
ClinPred		0.79	D
GERP RS		4.9
Varity_R		0.17
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-88383911;