chr10-73646383-A-C

Position:

• chr10-73646383-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO2L	NM_001114133.3	c.*335T>G		3_prime_UTR_variant	4/4	ENST00000394810.3	NP_001107605.1
SYNPO2L	NM_024875.5	c.*335T>G		3_prime_UTR_variant	2/2		NP_079151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO2L	ENST00000394810	c.*335T>G		3_prime_UTR_variant	4/4	1	NM_001114133.3	ENSP00000378289.2
SYNPO2L	ENST00000372873	c.*335T>G		3_prime_UTR_variant	2/2	1		ENSP00000361964.4

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

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.168

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

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.178

Alfa AF: 0.157 Hom.: 2238

Bravo AF: 0.221

Asia WGS AF: 0.177 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.6
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs3740293; hg19: chr10-75406141;