rs12601246

Variant names:

• chr17-1819019-C-T
• rs12601246
• NM_052928.3:c.135-6904G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052928.3(SMYD4):​c.135-6904G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,694 control chromosomes in the GnomAD database, including 2,779 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 0.19 (2779 hom., cov: 30)
• Consequence: SMYD4 NM_052928.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD4	NM_052928.3	c.135-6904G>A		intron_variant	Intron 2 of 10	ENST00000305513.12	NP_443160.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12	c.135-6904G>A		intron_variant	Intron 2 of 10	1	NM_052928.3	ENSP00000304360.7

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28570 AN: 151576 Hom.: 2783 Cov.: 30

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.188 AC: 28576 AN: 151694 Hom.: 2779 Cov.: 30 AF XY: 0.184 AC XY: 13663 AN XY: 74110

African (AFR) AF: 0.202 AC: 8336 AN: 41316

American (AMR) AF: 0.162 AC: 2463 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3472

East Asian (EAS) AF: 0.130 AC: 674 AN: 5168

South Asian (SAS) AF: 0.125 AC: 601 AN: 4802

European-Finnish (FIN) AF: 0.161 AC: 1695 AN: 10496

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13529 AN: 67922

Other (OTH) AF: 0.201 AC: 424 AN: 2110

Alfa AF: 0.194 Hom.: 1135

Bravo AF: 0.191

Asia WGS AF: 0.141 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.5
DANN	Benign	0.49
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12601246; hg19: chr17-1722313;