Variant 5-41142830-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000065.5(C6):c.2800G>A(p.Ala934Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,612,404 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 84 hom. )

Consequence

C6
NM_000065.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68

Variant links:

Genes affected

C6 (HGNC:1339): (complement C6) This gene encodes a component of the complement cascade. The encoded protein is part of the membrane attack complex that can be incorporated into the cell membrane and cause cell lysis. Mutations in this gene are associated with complement component-6 deficiency. Transcript variants encoding the same protein have been described.[provided by RefSeq, Nov 2012]

C6 links:

LOC105374739 (HGNC:):

LOC105374739 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022589564).

BP6

Variant 5-41142830-C-T is Benign according to our data. Variant chr5-41142830-C-T is described in ClinVar as [Benign]. Clinvar id is 1165368.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6	NM_000065.5 linkuse as main transcript	c.2800G>A	p.Ala934Thr	missense_variant	18/18	ENST00000337836.10
LOC105374739	XR_001742650.2 linkuse as main transcript	n.887-18483C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C6	ENST00000337836.10 linkuse as main transcript	c.2800G>A	p.Ala934Thr	missense_variant	18/18	1	NM_000065.5	P1
C6	ENST00000263413.7 linkuse as main transcript	c.2800G>A	p.Ala934Thr	missense_variant	18/18	1		P1
C6	ENST00000706654.1 linkuse as main transcript	n.967G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0377

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00337

AC:

845

AN:

250944

Hom.:

AF XY:

0.00335

AC XY:

454

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0390

Gnomad SAS exome

AF:

0.00336

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00195

AC:

2847

AN:

1460230

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1420

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0592

Gnomad4 SAS exome

AF:

0.00306

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.0000756

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00144

AC:

219

AN:

152174

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0376

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.00172

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00341

AC:

414

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.3

DANN

Benign

0.96

DEOGEN2

Benign

0.040

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.081

Sift

Benign

0.080

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0010

B;B

Vest4

0.061

MVP

0.067

MPC

0.034

ClinPred

0.027

GERP RS

-3.4

Varity_R

0.12

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