NM_001167740.2:c.702+118G>C

Variant names:

• chr1-245927813-C-G
• rs2275313
• NM_001167740.2:c.702+118G>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.702+118G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 717,602 control chromosomes in the GnomAD database, including 265,051 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 0.83 (53533 hom., cov: 31)
  • Exomes 𝑓: 0.86 (211518 hom.)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.702+118G>C		intron_variant	Intron 7 of 11	ENST00000490107.6	NP_001161212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.702+118G>C		intron_variant	Intron 7 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126663 AN: 151974 Hom.: 53508 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.832

GnomAD4 exome AF: 0.859 AC: 485548 AN: 565510 Hom.: 211518 AF XY: 0.856 AC XY: 260110 AN XY: 303884

African (AFR) AF: 0.735 AC: 11495 AN: 15646

American (AMR) AF: 0.869 AC: 28205 AN: 32448

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 16089 AN: 17940

East Asian (EAS) AF: 0.465 AC: 12949 AN: 27864

South Asian (SAS) AF: 0.801 AC: 50372 AN: 62912

European-Finnish (FIN) AF: 0.866 AC: 25409 AN: 29356

Middle Eastern (MID) AF: 0.896 AC: 2066 AN: 2306

European-Non Finnish (NFE) AF: 0.903 AC: 314601 AN: 348516

Other (OTH) AF: 0.854 AC: 24362 AN: 28522

GnomAD4 genome AF: 0.833 AC: 126732 AN: 152092 Hom.: 53533 Cov.: 31 AF XY: 0.831 AC XY: 61745 AN XY: 74342

African (AFR) AF: 0.739 AC: 30622 AN: 41452

American (AMR) AF: 0.875 AC: 13384 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3119 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2451 AN: 5144

South Asian (SAS) AF: 0.796 AC: 3839 AN: 4822

European-Finnish (FIN) AF: 0.864 AC: 9148 AN: 10590

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61316 AN: 68006

Other (OTH) AF: 0.828 AC: 1748 AN: 2112

Alfa AF: 0.865 Hom.: 7095

Bravo AF: 0.828

Asia WGS AF: 0.641 AC: 2233 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	0.020
DANN	Benign	0.36
PhyloP100		-0.91
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: rs2275313; hg19: chr1-246091115;