Variant 8-61299909-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173519.3(CLVS1):c.82G>T(p.Ala28Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLVS1
NM_173519.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

Variant links:

Genes affected

CLVS1 (HGNC:23139): (clavesin 1) Enables phosphatidylinositol-3,5-bisphosphate binding activity. Predicted to be involved in lysosome organization. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

CLVS1 links:

CLVS1 (HGNC:):

CLVS1 links:

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ACMG classification

Classification made for transcript

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=0.22019982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLVS1	NM_173519.3 linkuse as main transcript	c.82G>T	p.Ala28Ser	missense_variant	2/6	ENST00000325897.5	NP_775790.1
CLVS1	XM_017013141.2 linkuse as main transcript	c.82G>T	p.Ala28Ser	missense_variant	3/7		XP_016868630.1	Q8IUQ0-1
CLVS1	XM_017013142.3 linkuse as main transcript	c.82G>T	p.Ala28Ser	missense_variant	3/7		XP_016868631.1	Q8IUQ0-1
CLVS1	XM_024447079.2 linkuse as main transcript	c.82G>T	p.Ala28Ser	missense_variant	5/9		XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000325897.5 linkuse as main transcript	c.82G>T	p.Ala28Ser	missense_variant	2/6	1	NM_173519.3	ENSP00000325506.4		Q8IUQ0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727116

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 11, 2024

The c.82G>T (p.A28S) alteration is located in exon 2 (coding exon 1) of the CLVS1 gene. This alteration results from a G to T substitution at nucleotide position 82, causing the alanine (A) at amino acid position 28 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

T;T;T

Eigen

Benign

0.099

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;.;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.020

.;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.47

N;N;N

REVEL

Uncertain

0.36

Sift

Benign

0.15

T;T;T

Sift4G

Pathogenic

0.0

D;T;T

Polyphen

0.79

P;B;B

Vest4

0.22

MutPred

0.40

Gain of disorder (P = 0.0289);Gain of disorder (P = 0.0289);Gain of disorder (P = 0.0289);

MVP

0.42

MPC

0.37

ClinPred

0.67

GERP RS

5.8

Varity_R

0.11

gMVP

0.37

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over