1-245961981-C-T

Position:

• chr1-245961981-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.532-32044G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,886 control chromosomes in the GnomAD database, including 25,136 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 0.56 (25136 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.532-32044G>A		intron_variant		ENST00000490107.6	NP_001161212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.532-32044G>A		intron_variant		1	NM_001167740.2	ENSP00000419184	P1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85247 AN: 151768 Hom.: 25139 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.561 AC: 85271 AN: 151886 Hom.: 25136 Cov.: 31 AF XY: 0.556 AC XY: 41252 AN XY: 74236

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.590

Alfa AF: 0.629 Hom.: 40224

Bravo AF: 0.557

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.52

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: rs1544149; hg19: chr1-246125283;