17-1813981-A-C

Variant names:

• chr17-1813981-A-C
• rs12953068
• NM_052928.3:c.135-1866T>G

Variant summary

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

The NM_052928.3(SMYD4):​c.135-1866T>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
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052928.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD4	NM_052928.3	MANE Select	c.135-1866T>G		intron	N/A	NP_443160.2	Q8IYR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD4	ENST00000305513.12	TSL:1 MANE Select	c.135-1866T>G		intron	N/A	ENSP00000304360.7	Q8IYR2
	SMYD4	ENST00000954772.1		c.135-1866T>G		intron	N/A	ENSP00000624831.1
	SMYD4	ENST00000954774.1		c.135-1866T>G		intron	N/A	ENSP00000624833.1

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

African (AFR) AF: 0.927 AC: 38484 AN: 41528

American (AMR) AF: 0.601 AC: 9170 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2808 AN: 3470

East Asian (EAS) AF: 0.505 AC: 2605 AN: 5158

South Asian (SAS) AF: 0.572 AC: 2756 AN: 4814

European-Finnish (FIN) AF: 0.725 AC: 7651 AN: 10558

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56457 AN: 67976

Other (OTH) AF: 0.787 AC: 1661 AN: 2110

Alfa AF: 0.808 Hom.: 56134

Bravo AF: 0.801

Asia WGS AF: 0.514 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.61
PhyloP100		0.11
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: rs12953068; hg19: chr17-1717275; COSMIC: COSV59713327;