1-246215691-G-A

Variant names:

• chr1-246215691-G-A
• rs10924559
• NM_001167740.2:c.531+111510C>T

Variant summary

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

The NM_001167740.2(SMYD3):​c.531+111510C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,978 control chromosomes in the GnomAD database, including 2,760 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 0.18 (2760 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.531+111510C>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.531+111510C>T		intron_variant	Intron 5 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26903 AN: 151862 Hom.: 2757 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.177 AC: 26918 AN: 151978 Hom.: 2760 Cov.: 32 AF XY: 0.180 AC XY: 13352 AN XY: 74274

African (AFR) AF: 0.138 AC: 5696 AN: 41402

American (AMR) AF: 0.271 AC: 4143 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1761 AN: 5166

South Asian (SAS) AF: 0.231 AC: 1110 AN: 4802

European-Finnish (FIN) AF: 0.186 AC: 1969 AN: 10562

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10979 AN: 67982

Other (OTH) AF: 0.182 AC: 384 AN: 2112

Alfa AF: 0.152 Hom.: 978

Bravo AF: 0.188

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		0.92
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: rs10924559; hg19: chr1-246378993;