rs199668753

Variant names:

• chr17-1783096-C-A
• NM_052928.3:c.2200G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-1783096-C-A
• chr17-1783096-C-G
• chr17-1783096-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052928.3(SMYD4):​c.2200G>T​(p.Gly734Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SMYD4 NM_052928.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD4	NM_052928.3	c.2200G>T	p.Gly734Trp	missense_variant	Exon 10 of 11	ENST00000305513.12	NP_443160.2
SMYD4	XM_024450560.2	c.2200G>T	p.Gly734Trp	missense_variant	Exon 10 of 11		XP_024306328.1
SMYD4	XM_047435290.1	c.2200G>T	p.Gly734Trp	missense_variant	Exon 10 of 10		XP_047291246.1
SMYD4	XM_047435291.1	c.1888G>T	p.Gly630Trp	missense_variant	Exon 9 of 10		XP_047291247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12	c.2200G>T	p.Gly734Trp	missense_variant	Exon 10 of 11	1	NM_052928.3	ENSP00000304360.7
SMYD4	ENST00000491788.1	c.1612G>T	p.Gly538Trp	missense_variant	Exon 6 of 6	2		ENSP00000460921.1
SMYD4	ENST00000476292.1	n.*14G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461882 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.8	D;.
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.93
MutPred		0.48		Loss of disorder (P = 0.0041);.;
MVP		0.88
MPC		0.47
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.82
gMVP		0.79

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: chr17-1686390;