Variant 2-88084318-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_198274.4(SMYD1):c.140T>G(p.Leu47Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000637 in 1,412,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

SMYD1
NM_198274.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD1	NM_198274.4 linkuse as main transcript	c.140T>G	p.Leu47Arg	missense_variant, splice_region_variant	2/10	ENST00000419482.7	NP_938015.1	Q8NB12Q5HYE8
SMYD1	NM_001330364.2 linkuse as main transcript	c.140T>G	p.Leu47Arg	missense_variant, splice_region_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.140T>G	p.Leu47Arg	missense_variant, splice_region_variant	2/10	1	NM_198274.4	ENSP00000393453.2	Q8NB12
SMYD1	ENST00000444564.2 linkuse as main transcript	c.140T>G	p.Leu47Arg	missense_variant, splice_region_variant	2/9	5		ENSP00000407888.2	E9PHG3
SMYD1	ENST00000438570.1 linkuse as main transcript	c.140T>G	p.Leu47Arg	missense_variant, splice_region_variant	2/3	2		ENSP00000387482.1	C9JUP3
SMYD1	ENST00000468008.1 linkuse as main transcript	n.170T>G		splice_region_variant, non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249344

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000637

AC:

AN:

1412550

Hom.:

Cov.:

AF XY:

0.00000718

AC XY:

AN XY:

696146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000517

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000652

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jul 26, 2024

The c.140T>G (p.L47R) alteration is located in exon 2 (coding exon 2) of the SMYD1 gene. This alteration results from a T to G substitution at nucleotide position 140, causing the leucine (L) at amino acid position 47 to be replaced by an arginine (R). 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

0.23

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

T;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.79

D;D;D

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.89

N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.23

T;T;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.93

P;.;P

Vest4

0.73

MutPred

0.55

Loss of stability (P = 0.0371);Loss of stability (P = 0.0371);Loss of stability (P = 0.0371);

MVP

0.95

MPC

0.28

ClinPred

0.94

GERP RS

5.8

Varity_R

0.44

gMVP

0.77

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