2-88067874-G-A

Variant names:

• chr2-88067874-G-A
• NM_198274.4:c.10G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198274.4(SMYD1):​c.10G>A​(p.Gly4Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMYD1 NM_198274.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17626807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD1	NM_198274.4	c.10G>A	p.Gly4Arg	missense_variant	Exon 1 of 10	ENST00000419482.7	NP_938015.1
SMYD1	NM_001330364.2	c.10G>A	p.Gly4Arg	missense_variant	Exon 1 of 9		NP_001317293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD1	ENST00000419482.7	c.10G>A	p.Gly4Arg	missense_variant	Exon 1 of 10	1	NM_198274.4	ENSP00000393453.2
SMYD1	ENST00000444564.2	c.10G>A	p.Gly4Arg	missense_variant	Exon 1 of 9	5		ENSP00000407888.2
SMYD1	ENST00000438570.1	c.10G>A	p.Gly4Arg	missense_variant	Exon 1 of 3	2		ENSP00000387482.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461648 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727118

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.10G>A (p.G4R) alteration is located in exon 1 (coding exon 1) of the SMYD1 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the glycine (G) at amino acid position 4 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	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.98	N;N;N
REVEL	Benign	0.091
Sift	Benign	0.055	T;T;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.97	D;.;.
Vest4		0.23
MutPred		0.44		Gain of MoRF binding (P = 0.0094);Gain of MoRF binding (P = 0.0094);Gain of MoRF binding (P = 0.0094);
MVP		0.45
MPC		0.089
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.19
gMVP		0.56

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: chr2-88367393;