10-73647914-C-A

Variant names:

• chr10-73647914-C-A
• NM_001114133.3:c.1738G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114133.3(SYNPO2L):​c.1738G>T​(p.Ala580Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,376,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A580T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SYNPO2L NM_001114133.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15360233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNPO2L	NM_001114133.3	c.1738G>T	p.Ala580Ser	missense_variant	Exon 4 of 4	ENST00000394810.3	NP_001107605.1
SYNPO2L	NM_024875.5	c.1066G>T	p.Ala356Ser	missense_variant	Exon 2 of 2		NP_079151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNPO2L	ENST00000394810.3	c.1738G>T	p.Ala580Ser	missense_variant	Exon 4 of 4	1	NM_001114133.3	ENSP00000378289.2
SYNPO2L	ENST00000372873.8	c.1066G>T	p.Ala356Ser	missense_variant	Exon 2 of 2	1		ENSP00000361964.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1376228 Hom.: 0 Cov.: 35 AF XY: 0.00000148 AC XY: 1 AN XY: 676096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0063	.;T
Eigen	Benign	-0.083
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.020	N;N
REVEL	Benign	0.10
Sift	Benign	0.26	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.98	D;P
Vest4		0.15
MutPred		0.24		.;Gain of glycosylation at A580 (P = 0.0027);
MVP		0.50
MPC		1.1
ClinPred		0.69	D
GERP RS		5.0
Varity_R		0.098
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-75407672;