rs12953068

Positions:

• chr17-1813981-A-C
• chr17-1813981-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052928.3(SMYD4):​c.135-1866T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,070 control chromosomes in the GnomAD database, including 50,608 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50608 hom., cov: 32)
• Consequence: SMYD4 NM_052928.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD4	NM_052928.3	c.135-1866T>G		intron_variant		ENST00000305513.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD4	ENST00000305513.12	c.135-1866T>G		intron_variant		1	NM_052928.3	P1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122511 AN: 151952 Hom.: 50558 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 122617 AN: 152070 Hom.: 50608 Cov.: 32 AF XY: 0.793 AC XY: 58930 AN XY: 74320

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.787

Alfa AF: 0.805 Hom.: 46603

Bravo AF: 0.801

Asia WGS AF: 0.514 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs12953068; hg19: chr17-1717275; COSMIC: COSV59713327;