Variant chr12-4518843-A-G 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_020374.4(C12orf4):c.766T>C(p.Ser256Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,592,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

C12orf4
NM_020374.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

C12orf4 (HGNC:1184): (FERRY endosomal RAB5 effector complex subunit 3) This gene is highly conserved from nematodes to humans. In rat, the orthologous gene encodes a cytoplasmic protein that is involved in mast cell degranulation. The human gene has been implicated in autosomal recessive intellectual disability. [provided by RefSeq, Sep 2016]

C12orf4 links:

C12orf4 (HGNC:):

C12orf4 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=0.1274493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf4	NM_020374.4 linkuse as main transcript	c.766T>C	p.Ser256Pro	missense_variant	7/14	ENST00000261250.8	NP_065107.1	Q9NQ89

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
C12orf4	ENST00000261250.8 linkuse as main transcript	c.766T>C	p.Ser256Pro	missense_variant	7/14	1	NM_020374.4	ENSP00000261250.3	Q9NQ89
C12orf4	ENST00000545746.5 linkuse as main transcript	c.766T>C	p.Ser256Pro	missense_variant	7/14	1		ENSP00000439996.1	Q9NQ89
C12orf4	ENST00000541014.5 linkuse as main transcript	c.247T>C	p.Ser83Pro	missense_variant	6/8	5		ENSP00000440820.1	F5GXX6
C12orf4	ENST00000544697.1 linkuse as main transcript	n.210-588T>C		intron_variant		5		ENSP00000439471.1	F5H271

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000235

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000173

AC:

AN:

237534

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

128494

show subpopulations

Gnomad AFR exome

AF:

0.0000656

Gnomad AMR exome

AF:

0.000375

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:

0.000248

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.000266

AC:

383

AN:

1440694

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

181

AN XY:

716230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.000564

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.000270

GnomAD4 genome

AF:

0.000164

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.000166

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal recessive 66

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

May 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.69

.;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.86

L;L;.

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.20

T;T;T

Sift4G

Uncertain

0.037

D;D;T

Polyphen

0.92

P;P;.

Vest4

0.15

MVP

0.37

MPC

0.45

ClinPred

0.050

GERP RS

4.0

Varity_R

0.070

gMVP

0.43

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