NM_001167740.2:c.531+171021T>C

Variant names:

• chr1-246156180-A-G
• rs4654092
• NM_001167740.2:c.531+171021T>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.531+171021T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,918 control chromosomes in the GnomAD database, including 24,986 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 0.52 (24986 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.531+171021T>C		intron_variant	Intron 5 of 11	ENST00000490107.6	NP_001161212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.531+171021T>C		intron_variant	Intron 5 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78745 AN: 151798 Hom.: 24988 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.518 AC: 78750 AN: 151918 Hom.: 24986 Cov.: 31 AF XY: 0.507 AC XY: 37616 AN XY: 74264

African (AFR) AF: 0.200 AC: 8305 AN: 41440

American (AMR) AF: 0.531 AC: 8109 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2397 AN: 3470

East Asian (EAS) AF: 0.0547 AC: 283 AN: 5174

South Asian (SAS) AF: 0.358 AC: 1717 AN: 4796

European-Finnish (FIN) AF: 0.628 AC: 6615 AN: 10530

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49261 AN: 67936

Other (OTH) AF: 0.554 AC: 1165 AN: 2102

Alfa AF: 0.652 Hom.: 26785

Bravo AF: 0.496

Asia WGS AF: 0.213 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.60
PhyloP100		0.81
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: rs4654092; hg19: chr1-246319482;