1-245842496-C-A

Variant names:

• chr1-245842496-C-A
• rs9728248
• NM_001167740.2:c.1076+16000G>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.1076+16000G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,916 control chromosomes in the GnomAD database, including 10,532 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 0.35 (10532 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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.1076+16000G>T		intron	N/A	NP_001161212.1
	SMYD3	NM_001375962.1		c.965+16000G>T		intron	N/A	NP_001362891.1
	SMYD3	NM_001375963.1		c.899+16000G>T		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.1076+16000G>T		intron	N/A	ENSP00000419184.2
	SMYD3	ENST00000366516.5	TSL:1	n.1431+16000G>T		intron	N/A
	SMYD3	ENST00000366517.5	TSL:1	n.940+16000G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53018 AN: 151798 Hom.: 10502 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.350 AC: 53095 AN: 151916 Hom.: 10532 Cov.: 32 AF XY: 0.360 AC XY: 26720 AN XY: 74232

African (AFR) AF: 0.297 AC: 12286 AN: 41406

American (AMR) AF: 0.427 AC: 6513 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3468

East Asian (EAS) AF: 0.864 AC: 4458 AN: 5162

South Asian (SAS) AF: 0.636 AC: 3053 AN: 4802

European-Finnish (FIN) AF: 0.352 AC: 3709 AN: 10542

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.307 AC: 20840 AN: 67954

Other (OTH) AF: 0.340 AC: 717 AN: 2110

Alfa AF: 0.335 Hom.: 4864

Bravo AF: 0.352

Asia WGS AF: 0.703 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.69
PhyloP100		-0.71
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: rs9728248; hg19: chr1-246005798;