rs375624525

Variant names:

• chr17-1786902-C-A
• rs375624525
• NM_052928.3:c.1792G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-1786902-C-A
• chr17-1786902-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052928.3(SMYD4):​c.1792G>T​(p.Ala598Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SMYD4 NM_052928.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026798248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD4	NM_052928.3	c.1792G>T	p.Ala598Ser	missense_variant	Exon 7 of 11	ENST00000305513.12	NP_443160.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12	c.1792G>T	p.Ala598Ser	missense_variant	Exon 7 of 11	1	NM_052928.3	ENSP00000304360.7
SMYD4	ENST00000491788.1	c.1204G>T	p.Ala402Ser	missense_variant	Exon 3 of 6	2		ENSP00000460921.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251420 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461868 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.54
DANN	Benign	0.67
DEOGEN2	Benign	0.0025	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.090	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.027	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.8	N;.
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.99	N;.
REVEL	Benign	0.18
Sift	Benign	0.77	T;.
Sift4G	Benign	0.74	T;T
Polyphen		0.0020	B;.
Vest4		0.087
MutPred		0.35		Gain of disorder (P = 0.083);.;
MVP		0.42
MPC		0.070
ClinPred		0.021	T
GERP RS		-11
Varity_R		0.021
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs375624525; hg19: chr17-1690196;