1-245830733-G-T

Variant names:

• chr1-245830733-G-T
• rs7514038
• NM_001167740.2:c.1076+27763C>A

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+27763C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,134 control chromosomes in the GnomAD database, including 51,402 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 0.80 (51402 hom., cov: 32)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD3	NM_001167740.2	c.1076+27763C>A		intron_variant	Intron 10 of 11	ENST00000490107.6	NP_001161212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD3	ENST00000490107.6	c.1076+27763C>A		intron_variant	Intron 10 of 11	1	NM_001167740.2	ENSP00000419184.2

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122026 AN: 152016 Hom.: 51381 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.803 AC: 122089 AN: 152134 Hom.: 51402 Cov.: 32 AF XY: 0.802 AC XY: 59676 AN XY: 74388

African (AFR) AF: 0.546 AC: 22637 AN: 41446

American (AMR) AF: 0.723 AC: 11070 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3332 AN: 3472

East Asian (EAS) AF: 0.686 AC: 3534 AN: 5152

South Asian (SAS) AF: 0.852 AC: 4103 AN: 4816

European-Finnish (FIN) AF: 0.958 AC: 10169 AN: 10616

Middle Eastern (MID) AF: 0.863 AC: 252 AN: 292

European-Non Finnish (NFE) AF: 0.947 AC: 64389 AN: 68012

Other (OTH) AF: 0.829 AC: 1754 AN: 2116

Alfa AF: 0.906 Hom.: 68465

Bravo AF: 0.771

Asia WGS AF: 0.745 AC: 2593 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	0.86
DANN	Benign	0.68
PhyloP100		-0.47
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: rs7514038; hg19: chr1-245994035; COSMIC: COSV107460217;