1-245802249-A-G

Variant names:

• chr1-245802249-A-G
• rs2791398
• NM_001167740.2:c.1077-38100T>C

Variant summary

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

The NM_001167740.2(SMYD3):​c.1077-38100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,196 control chromosomes in the GnomAD database, including 60,574 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 0.89 (60574 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167740.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD3	NM_001167740.2	MANE Select	c.1077-38100T>C		intron	N/A	NP_001161212.1
	SMYD3	NM_001375962.1		c.966-38100T>C		intron	N/A	NP_001362891.1
	SMYD3	NM_001375963.1		c.900-38100T>C		intron	N/A	NP_001362892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD3	ENST00000490107.6	TSL:1 MANE Select	c.1077-38100T>C		intron	N/A	ENSP00000419184.2
	SMYD3	ENST00000366516.5	TSL:1	n.1432-38100T>C		intron	N/A
	SMYD3	ENST00000366517.5	TSL:1	n.941-38100T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135322 AN: 152078 Hom.: 60517 Cov.: 31

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.890 AC: 135435 AN: 152196 Hom.: 60574 Cov.: 31 AF XY: 0.885 AC XY: 65804 AN XY: 74388

African (AFR) AF: 0.970 AC: 40313 AN: 41552

American (AMR) AF: 0.833 AC: 12732 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2904 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4655 AN: 5172

South Asian (SAS) AF: 0.930 AC: 4471 AN: 4808

European-Finnish (FIN) AF: 0.768 AC: 8129 AN: 10590

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59273 AN: 68008

Other (OTH) AF: 0.889 AC: 1876 AN: 2110

Alfa AF: 0.877 Hom.: 100466

Bravo AF: 0.895

Asia WGS AF: 0.916 AC: 3184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.40
PhyloP100		-0.72
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: rs2791398; hg19: chr1-245965551;