rs3740293

Variant names:

• chr10-73646383-A-C
• rs3740293
• NM_001114133.3:c.*335T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001114133.3(SYNPO2L):​c.*335T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,034,624 control chromosomes in the GnomAD database, including 14,696 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 0.21 (4262 hom., cov: 31)
  • Exomes 𝑓: 0.15 (10434 hom.)
• Consequence: SYNPO2L NM_001114133.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517
• Publications: 21 publications found

Genes affected

SYNPO2L (HGNC:23532): (synaptopodin 2 like) Predicted to enable actin binding activity. Predicted to be involved in several processes, including positive regulation of Rho protein signal transduction; positive regulation of stress fiber assembly; and sarcomere organization. Located in cell junction; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114133.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2L	NM_001114133.3	MANE Select	c.*335T>G		3_prime_UTR	Exon 4 of 4	NP_001107605.1	Q9H987-1
	SYNPO2L	NM_024875.5		c.*335T>G		3_prime_UTR	Exon 2 of 2	NP_079151.2	Q9H987-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2L	ENST00000394810.3	TSL:1 MANE Select	c.*335T>G		3_prime_UTR	Exon 4 of 4	ENSP00000378289.2	Q9H987-1
	SYNPO2L	ENST00000372873.8	TSL:1	c.*335T>G		3_prime_UTR	Exon 2 of 2	ENSP00000361964.4	Q9H987-2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32029 AN: 151854 Hom.: 4255 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.149 AC: 131206 AN: 882652 Hom.: 10434 Cov.: 34 AF XY: 0.148 AC XY: 60737 AN XY: 409526

African (AFR) AF: 0.382 AC: 6723 AN: 17622

American (AMR) AF: 0.119 AC: 326 AN: 2740

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 1536 AN: 7078

East Asian (EAS) AF: 0.211 AC: 1474 AN: 6988

South Asian (SAS) AF: 0.221 AC: 3785 AN: 17100

European-Finnish (FIN) AF: 0.139 AC: 416 AN: 2992

Middle Eastern (MID) AF: 0.175 AC: 331 AN: 1892

European-Non Finnish (NFE) AF: 0.140 AC: 111474 AN: 795616

Other (OTH) AF: 0.168 AC: 5141 AN: 30624

GnomAD4 genome AF: 0.211 AC: 32067 AN: 151972 Hom.: 4262 Cov.: 31 AF XY: 0.208 AC XY: 15432 AN XY: 74288

African (AFR) AF: 0.378 AC: 15669 AN: 41416

American (AMR) AF: 0.131 AC: 1994 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1053 AN: 5172

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4824

European-Finnish (FIN) AF: 0.134 AC: 1410 AN: 10560

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9580 AN: 67964

Other (OTH) AF: 0.178 AC: 374 AN: 2106

Alfa AF: 0.165 Hom.: 3307

Bravo AF: 0.221

Asia WGS AF: 0.177 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.6
DANN	Benign	0.83
PhyloP100		0.52
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: rs3740293; hg19: chr10-75406141;