Genetic Variant C6orf52:p.Gly44Ser (chr6-10687106-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145020.3(C6orf52):c.130G>A(p.Gly44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000844 in 1,552,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000089 ( 1 hom. )

Consequence

C6orf52
NM_001145020.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.630

Publications

0 publications found

Variant links:

Genes affected

C6orf52 (HGNC:20881): (chromosome 6 open reading frame 52)

C6orf52 links:

ENSG00000285763 (HGNC:):

ENSG00000285763 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018161476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145020.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C6orf52	NM_001145020.3	MANE Select	c.130G>A	p.Gly44Ser	missense	Exon 3 of 5	NP_001138492.1	Q5T4I8-1
C6orf52	NM_001388310.1		c.130G>A	p.Gly44Ser	missense	Exon 3 of 6	NP_001375239.1
C6orf52	NM_001388311.1		c.112G>A	p.Gly38Ser	missense	Exon 3 of 6	NP_001375240.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C6orf52	ENST00000259983.8	TSL:5 MANE Select	c.130G>A	p.Gly44Ser	missense	Exon 3 of 5	ENSP00000259983.3	Q5T4I8-1
C6orf52	ENST00000896013.1		c.130G>A	p.Gly44Ser	missense	Exon 3 of 6	ENSP00000566072.1
C6orf52	ENST00000426700.6	TSL:2	c.130G>A	p.Gly44Ser	missense	Exon 2 of 4	ENSP00000410749.2	Q5T4I8-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

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

GnomAD2 exomes

AF:

0.000108

AC:

AN:

158128

AF XY:

0.0000839

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00156

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000893

AC:

125

AN:

1399740

Hom.:

Cov.:

AF XY:

0.0000724

AC XY:

AN XY:

690352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31600

American (AMR)

AF:

0.00

AC:

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00350

AC:

125

AN:

35740

South Asian (SAS)

AF:

0.00

AC:

AN:

79226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079022

Other (OTH)

AF:

0.00

AC:

AN:

58120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.039

M_CAP

Benign

0.0047

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

PhyloP100

0.63

PROVEAN

Benign

-0.99

REVEL

Benign

0.050

Sift

Benign

0.15

Sift4G

Benign

0.44

Polyphen

0.23

Vest4

0.16

MutPred

0.27

Gain of helix (P = 0.0425)

MVP

0.076

ClinPred

0.046

GERP RS

1.1

PromoterAI

-0.010

Neutral

(source)

Varity_R

0.084

gMVP

0.078

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over