NM_052928.3:c.1798C>G

Variant names:

• chr17-1786896-G-C
• NM_052928.3:c.1798C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052928.3(SMYD4):​c.1798C>G​(p.Pro600Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMYD4 NM_052928.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13631058).

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.1798C>G	p.Pro600Ala	missense	Exon 7 of 11	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.1798C>G	p.Pro600Ala	missense	Exon 7 of 11	ENSP00000304360.7	Q8IYR2
	SMYD4	ENST00000954772.1		c.1798C>G	p.Pro600Ala	missense	Exon 7 of 11	ENSP00000624831.1
	SMYD4	ENST00000954774.1		c.1798C>G	p.Pro600Ala	missense	Exon 7 of 11	ENSP00000624833.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.81
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.13
Sift	Benign	0.51	T
Sift4G	Benign	0.73	T
Polyphen		0.11	B
Vest4		0.21
MutPred		0.31		Loss of helix (P = 0.079)
MVP		0.76
MPC		0.074
ClinPred		0.083	T
GERP RS		2.9
Varity_R		0.020
gMVP		0.35
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr17-1690190;