rs4654180

Variant names:

• chr1-245985489-C-A
• rs4654180
• NM_001167740.2:c.532-55552G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-245985489-C-A
• chr1-245985489-C-G

Variant summary

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

The NM_001167740.2(SMYD3):​c.532-55552G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,120 control chromosomes in the GnomAD database, including 1,012 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 0.11 (1012 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 5 publications found

Genes affected

SMYD3 (HGNC:15513): (SET and MYND domain containing 3) This gene encodes a histone methyltransferase which functions in RNA polymerase II complexes by an interaction with a specific RNA helicase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

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 (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.532-55552G>T		intron_variant	Intron 5 of 11	ENST00000490107.6	NP_001161212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.532-55552G>T		intron_variant	Intron 5 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16682 AN: 152002 Hom.: 1007 Cov.: 31

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16693 AN: 152120 Hom.: 1012 Cov.: 31 AF XY: 0.114 AC XY: 8474 AN XY: 74388

African (AFR) AF: 0.0670 AC: 2779 AN: 41500

American (AMR) AF: 0.161 AC: 2459 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 470 AN: 3468

East Asian (EAS) AF: 0.0993 AC: 513 AN: 5168

South Asian (SAS) AF: 0.229 AC: 1099 AN: 4808

European-Finnish (FIN) AF: 0.114 AC: 1208 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7844 AN: 67984

Other (OTH) AF: 0.116 AC: 245 AN: 2112

Alfa AF: 0.112 Hom.: 1952

Bravo AF: 0.109

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-0.52
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: rs4654180; hg19: chr1-246148791;