Variant 2-88084423-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198274.4(SMYD1):c.245C>T(p.Ala82Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMYD1
NM_198274.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD1	NM_198274.4 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	2/10	ENST00000419482.7	NP_938015.1	Q8NB12Q5HYE8
SMYD1	NM_001330364.2 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	2/9		NP_001317293.1	E9PHG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMYD1	ENST00000419482.7 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	2/10	1	NM_198274.4	ENSP00000393453.2	Q8NB12
SMYD1	ENST00000444564.2 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	2/9	5		ENSP00000407888.2	E9PHG3
SMYD1	ENST00000438570.1 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	2/3	2		ENSP00000387482.1	C9JUP3
SMYD1	ENST00000468008.1 linkuse as main transcript	n.275C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723664

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.245C>T (p.A82V) 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 245, causing the alanine (A) at amino acid position 82 to be replaced by a valine (V). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

D;.;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.97

D;D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0030

D;D;T

Sift4G

Uncertain

0.029

D;D;T

Polyphen

0.97

D;.;D

Vest4

0.64

MutPred

0.64

Loss of catalytic residue at A82 (P = 0.0166);Loss of catalytic residue at A82 (P = 0.0166);Loss of catalytic residue at A82 (P = 0.0166);

MVP

0.37

MPC

0.40

ClinPred

0.99

GERP RS

5.6

Varity_R

0.68

gMVP

0.82

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over