Variant 12-4517141-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020374.4(C12orf4):c.1082T>C(p.Ile361Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,594,086 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 9 hom. )

Consequence

C12orf4
NM_020374.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006860733).

BP6

Variant 12-4517141-A-G is Benign according to our data. Variant chr12-4517141-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 723335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00065 (99/152296) while in subpopulation SAS AF= 0.00581 (28/4818). AF 95% confidence interval is 0.00413. There are 0 homozygotes in gnomad4. There are 56 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf4	NM_020374.4 linkuse as main transcript	c.1082T>C	p.Ile361Thr	missense_variant	9/14	ENST00000261250.8	NP_065107.1	Q9NQ89

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf4	ENST00000261250.8 linkuse as main transcript	c.1082T>C	p.Ile361Thr	missense_variant	9/14	1	NM_020374.4	ENSP00000261250.3		Q9NQ89

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00145

AC:

347

AN:

239944

Hom.:

AF XY:

0.00187

AC XY:

243

AN XY:

129912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00662

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000351

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

AF:

0.000797

AC:

1149

AN:

1441790

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

727

AN XY:

716498

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000404

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00649

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000197

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.000650

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000753

Hom.:

Bravo

AF:

0.000680

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00146

AC:

177

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	FERRY3: BP4 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.8

L;L;.

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.047

D;D;D

Polyphen

0.077

B;B;.

Vest4

0.68

MVP

0.37

MPC

0.61

ClinPred

0.11

GERP RS

4.9

Varity_R

0.26

gMVP

0.67

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