Variant 15-88855595-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001369268.1(ACAN):c.3010A>T(p.Thr1004Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 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. T1004A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 8)

Exomes 𝑓: 0.00019 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

ACAN
NM_001369268.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.266

Variant links:

Genes affected

ACAN (HGNC:319): (aggrecan) This gene is a member of the aggrecan/versican proteoglycan family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage. Mutations in this gene may be involved in skeletal dysplasia and spinal degeneration. Multiple alternatively spliced transcript variants that encode different protein isoforms have been observed in this gene. [provided by RefSeq, Jul 2008]

ACAN links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031533152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAN	NM_001369268.1 linkuse as main transcript	c.3010A>T	p.Thr1004Ser	missense_variant	12/19	ENST00000560601.4	NP_001356197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAN	ENST00000560601.4 linkuse as main transcript	c.3010A>T	p.Thr1004Ser	missense_variant	12/19	3	NM_001369268.1	ENSP00000453581.2		H0YMF1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

44986

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000190

AC:

AN:

194564

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

105248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000306

Gnomad4 ASJ exome

AF:

0.000416

Gnomad4 EAS exome

AF:

0.0000624

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000567

Gnomad4 NFE exome

AF:

0.000259

Gnomad4 OTH exome

AF:

0.000492

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

45028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22086

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.18

DANN

Benign

0.10

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.40

T;T;T;T;T;.

M_CAP

Benign

0.030

MetaRNN

Benign

0.032

T;T;T;T;T;T

MetaSVM

Benign

-0.57

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.76

.;N;.;N;N;N

REVEL

Benign

0.23

Sift

Benign

1.0

.;T;.;T;T;T

Sift4G

Benign

1.0

.;T;T;T;T;T

Vest4

0.025, 0.039, 0.027, 0.024, 0.028

MutPred

0.31

Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);.;Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);

MVP

0.093

MPC

0.18

ClinPred

0.050

GERP RS

-1.5

Varity_R

0.017

gMVP

0.039

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over