7-36390047-G-A

Variant summary

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

The ENST00000297063.10(MATCAP2):c.28C>T(p.His10Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MATCAP2
ENST00000297063.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

Variant links:

Genes affected

MATCAP2 (HGNC:22206): (microtubule associated tyrosine carboxypeptidase 2)

MATCAP2 links:

ANLN (HGNC:14082): (anillin, actin binding protein) This gene encodes an actin-binding protein that plays a role in cell growth and migration, and in cytokinesis. The encoded protein is thought to regulate actin cytoskeletal dynamics in podocytes, components of the glomerulus. Mutations in this gene are associated with focal segmental glomerulosclerosis 8. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ANLN links:

Genome browser will be placed here

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=0.11645919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANLN	NM_018685.5 linkuse as main transcript	c.18+3G>A		splice_donor_region_variant, intron_variant		ENST00000265748.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATCAP2	ENST00000297063.10 linkuse as main transcript	c.28C>T	p.His10Tyr	missense_variant	1/7	1			Q8NCT3-1
ANLN	ENST00000265748.7 linkuse as main transcript	c.18+3G>A		splice_donor_region_variant, intron_variant		1	NM_018685.5	P2	Q9NQW6-1
ANLN	ENST00000396068.6 linkuse as main transcript	c.18+3G>A		splice_donor_region_variant, intron_variant		1		A2	Q9NQW6-2
MATCAP2	ENST00000429651.1 linkuse as main transcript	c.28C>T	p.His10Tyr	missense_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251328

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727056

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:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

May 04, 2021

Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with ANLN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 1 of the ANLN gene. It does not directly change the encoded amino acid sequence of the ANLN protein. It affects a nucleotide within the consensus splice site of the intron. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.063

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;.

Polyphen

0.0

B;.

Vest4

0.41

MutPred

0.18

Loss of methylation at R6 (P = 0.1203);Loss of methylation at R6 (P = 0.1203);

MVP

0.13

MPC

0.42

ClinPred

0.49

GERP RS

2.0

Varity_R

0.19

gMVP

0.018

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over