chr17-1782554-C-G

Variant names:

• chr17-1782554-C-G
• rs4474730
• NM_052928.3:c.2261+481G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052928.3(SMYD4):​c.2261+481G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 27)
• Consequence: SMYD4 NM_052928.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 12 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD4	NM_052928.3	c.2261+481G>C		intron_variant	Intron 10 of 10	ENST00000305513.12	NP_443160.2
SMYD4	XM_024450560.2	c.2261+481G>C		intron_variant	Intron 10 of 10		XP_024306328.1
SMYD4	XM_047435291.1	c.1949+481G>C		intron_variant	Intron 9 of 9		XP_047291247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12	c.2261+481G>C		intron_variant	Intron 10 of 10	1	NM_052928.3	ENSP00000304360.7
SMYD4	ENST00000491788.1	c.*477G>C		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000460921.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 2268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.55
PhyloP100		0.52

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: rs4474730; hg19: chr17-1685848;