rs6693295

Variant names:

• chr1-246059818-C-T
• rs6693295
• NM_001167740.2:c.532-129881G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001167740.2(SMYD3):​c.532-129881G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,974 control chromosomes in the GnomAD database, including 5,194 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 0.25 (5194 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.532-129881G>A		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.532-129881G>A		intron_variant	Intron 5 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37411 AN: 151856 Hom.: 5187 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.246 AC: 37444 AN: 151974 Hom.: 5194 Cov.: 32 AF XY: 0.250 AC XY: 18590 AN XY: 74288

African (AFR) AF: 0.343 AC: 14191 AN: 41422

American (AMR) AF: 0.292 AC: 4453 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2028 AN: 5160

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4820

European-Finnish (FIN) AF: 0.221 AC: 2327 AN: 10538

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11677 AN: 67980

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.206 Hom.: 10806

Bravo AF: 0.261

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.58
PhyloP100		1.3
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: rs6693295; hg19: chr1-246223120;