rs11062

Positions:

• chr17-1779718-G-A

Variant summary

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

The NM_052928.3(SMYD4):​c.*1568C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,194 control chromosomes in the GnomAD database, including 10,976 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 0.38 (10970 hom., cov: 33)
  • Exomes 𝑓: 0.39 (6 hom.)
• Consequence: SMYD4 NM_052928.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD4	NM_052928.3	c.*1568C>T		3_prime_UTR_variant	11/11	ENST00000305513.12	NP_443160.2
SMYD4	XM_024450560.2	c.*1568C>T		3_prime_UTR_variant	11/11		XP_024306328.1
SMYD4	XM_047435291.1	c.*1568C>T		3_prime_UTR_variant	10/10		XP_047291247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513	c.*1568C>T		3_prime_UTR_variant	11/11	1	NM_052928.3	ENSP00000304360.7

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57004 AN: 151984 Hom.: 10954 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.391 AC: 36 AN: 92 Hom.: 6 Cov.: 0 AF XY: 0.407 AC XY: 22 AN XY: 54

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.375 AC: 57062 AN: 152102 Hom.: 10970 Cov.: 33 AF XY: 0.381 AC XY: 28321 AN XY: 74346

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.357

Alfa AF: 0.344 Hom.: 18850

Bravo AF: 0.379

Asia WGS AF: 0.476 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.72

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: rs11062; hg19: chr17-1683012; COSMIC: COSV54615695; COSMIC: COSV54615695;