Variant 2-88084422-G-A 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.244G>A(p.Ala82Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,334 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SMYD1
NM_198274.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

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.244G>A	p.Ala82Thr	missense_variant	2/10	ENST00000419482.7	NP_938015.1	Q8NB12Q5HYE8
SMYD1	NM_001330364.2 linkuse as main transcript	c.244G>A	p.Ala82Thr	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.244G>A	p.Ala82Thr	missense_variant	2/10	1	NM_198274.4	ENSP00000393453.2	Q8NB12
SMYD1	ENST00000444564.2 linkuse as main transcript	c.244G>A	p.Ala82Thr	missense_variant	2/9	5		ENSP00000407888.2	E9PHG3
SMYD1	ENST00000438570.1 linkuse as main transcript	c.244G>A	p.Ala82Thr	missense_variant	2/3	2		ENSP00000387482.1	C9JUP3
SMYD1	ENST00000468008.1 linkuse as main transcript	n.274G>A		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251480

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456334

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723930

show subpopulations

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:

0.0000166

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

Dec 04, 2024

The c.244G>A (p.A82T) alteration is located in exon 2 (coding exon 2) of the SMYD1 gene. This alteration results from a G to A substitution at nucleotide position 244, causing the alanine (A) at amino acid position 82 to be replaced by a threonine (T). 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

0.62

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

T;.;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.2

M;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0030

D;D;T

Sift4G

Uncertain

0.033

D;D;T

Polyphen

0.88

P;.;D

Vest4

0.60

MutPred

0.51

Loss of catalytic residue at A82 (P = 0.0016);Loss of catalytic residue at A82 (P = 0.0016);Loss of catalytic residue at A82 (P = 0.0016);

MVP

0.47

MPC

0.39

ClinPred

0.95

GERP RS

5.6

Varity_R

0.28

gMVP

0.76

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