1-246497934-C-T

Position:

• chr1-246497934-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167740.2(SMYD3):​c.164+9120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,518 control chromosomes in the GnomAD database, including 7,361 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 0.31 (7361 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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]

SMYD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.164+9120G>A		intron_variant		ENST00000490107.6	NP_001161212.1
SMYD3	NM_001375962.1	c.164+9120G>A		intron_variant			NP_001362891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.164+9120G>A		intron_variant		1	NM_001167740.2	ENSP00000419184.2
SMYD3	ENST00000403792.7	c.164+9120G>A		intron_variant		1		ENSP00000385380.3
SMYD3	ENST00000462422.5	n.91+9120G>A		intron_variant		5
SMYD3	ENST00000470863.1	n.179+9120G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46495 AN: 151406 Hom.: 7349 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.0578

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.307 AC: 46530 AN: 151518 Hom.: 7361 Cov.: 32 AF XY: 0.303 AC XY: 22408 AN XY: 74042

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.0579

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.326

Alfa AF: 0.340 Hom.: 8992

Bravo AF: 0.300

Asia WGS AF: 0.160 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs11800820; hg19: chr1-246661236;