1-246449831-C-T

Variant names:

• chr1-246449831-C-T
• rs7527610
• NM_001167740.2:c.164+57223G>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.164+57223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,188 control chromosomes in the GnomAD database, including 66,336 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 0.93 (66336 hom., cov: 31)
• Consequence: SMYD3 NM_001167740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 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.164+57223G>A		intron	N/A	NP_001161212.1
	SMYD3	NM_001375962.1		c.164+57223G>A		intron	N/A	NP_001362891.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD3	ENST00000490107.6	TSL:1 MANE Select	c.164+57223G>A		intron	N/A	ENSP00000419184.2
	SMYD3	ENST00000403792.7	TSL:1	c.164+57223G>A		intron	N/A	ENSP00000385380.3
	SMYD3	ENST00000455277.2	TSL:5	c.-14+33604G>A		intron	N/A	ENSP00000394281.1

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141489 AN: 152070 Hom.: 66295 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.939

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

GnomAD4 genome AF: 0.930 AC: 141586 AN: 152188 Hom.: 66336 Cov.: 31 AF XY: 0.930 AC XY: 69220 AN XY: 74400

African (AFR) AF: 0.804 AC: 33330 AN: 41478

American (AMR) AF: 0.970 AC: 14835 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3273 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4972 AN: 5174

South Asian (SAS) AF: 0.893 AC: 4307 AN: 4822

European-Finnish (FIN) AF: 0.996 AC: 10558 AN: 10604

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67158 AN: 68030

Other (OTH) AF: 0.937 AC: 1977 AN: 2110

Alfa AF: 0.961 Hom.: 28364

Bravo AF: 0.925

Asia WGS AF: 0.907 AC: 3156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.025
DANN	Benign	0.34
PhyloP100		-1.1
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: rs7527610; hg19: chr1-246613133;