NM_052928.3:c.1933G>C

Variant names:

• chr17-1784413-C-G
• NM_052928.3:c.1933G>C

Variant summary

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

The NM_052928.3(SMYD4):​c.1933G>C​(p.Val645Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMYD4 NM_052928.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

Genes affected

SMYD4 (HGNC:21067): (SET and MYND domain containing 4) Predicted to enable metal ion binding activity and methyltransferase activity. Involved in heart development. Predicted to be located in cytoplasm and 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=0.08205527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD4	NM_052928.3	c.1933G>C	p.Val645Leu	missense_variant	Exon 8 of 11	ENST00000305513.12	NP_443160.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12	c.1933G>C	p.Val645Leu	missense_variant	Exon 8 of 11	1	NM_052928.3	ENSP00000304360.7
SMYD4	ENST00000491788.1	c.1345G>C	p.Val449Leu	missense_variant	Exon 4 of 6	2		ENSP00000460921.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727238

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.7
DANN	Benign	0.84
DEOGEN2	Benign	0.0038	T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.50	N;.
REVEL	Benign	0.015
Sift	Benign	0.20	T;.
Sift4G	Benign	0.17	T;T
Polyphen		0.16	B;.
Vest4		0.21
MutPred		0.19		Loss of helix (P = 0.1299);.;
MVP		0.28
MPC		0.080
ClinPred		0.086	T
GERP RS		0.16
Varity_R		0.069
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr17-1687707;