Genetic Variant C17orf78:p.Thr152Ser (chr17-37386072-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173625.5(C17orf78):c.455C>G(p.Thr152Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,594,294 control chromosomes in the GnomAD database, including 40,578 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4338 hom., cov: 32)

Exomes 𝑓: 0.21 ( 36240 hom. )

Consequence

C17orf78
NM_173625.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.110

Publications

31 publications found

Variant links:

Genes affected

C17orf78 (HGNC:26831): (chromosome 17 open reading frame 78) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C17orf78 links:

ACACA (HGNC:84): (acetyl-CoA carboxylase alpha) Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACACA Gene-Disease associations (from GenCC):

acetyl-coa carboxylase deficiency
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACACA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1739079E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C17orf78	NM_173625.5 link	c.455C>G	p.Thr152Ser	missense_variant	Exon 4 of 7	ENST00000615133.2	NP_775896.3	Q8N4C9-1
ACACA	NM_198834.3 link	c.38+20190G>C		intron_variant	Intron 1 of 55	ENST00000616317.5	NP_942131.1	Q13085-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C17orf78	ENST00000615133.2 link	c.455C>G	p.Thr152Ser	missense_variant	Exon 4 of 7	1	NM_173625.5	ENSP00000478886.1	Q8N4C9-1
ACACA	ENST00000616317.5 link	c.38+20190G>C		intron_variant	Intron 1 of 55	1	NM_198834.3	ENSP00000483300.1	Q13085-4
C17orf78	ENST00000611038.4 link	c.392-3174C>G		intron_variant	Intron 3 of 4	2		ENSP00000477816.1	Q8N4C9-2

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34578

AN:

151942

Hom.:

4324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.209

GnomAD2 exomes

AF:

0.251

AC:

60489

AN:

241222

AF XY:

0.248

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.325

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.543

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.209

AC:

301465

AN:

1442234

Hom.:

36240

Cov.:

AF XY:

0.212

AC XY:

152095

AN XY:

717682

show subpopulations

African (AFR)

AF:

0.243

AC:

8020

AN:

32976

American (AMR)

AF:

0.315

AC:

13707

AN:

43470

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4754

AN:

25802

East Asian (EAS)

AF:

0.552

AC:

21696

AN:

39296

South Asian (SAS)

AF:

0.328

AC:

27527

AN:

83848

European-Finnish (FIN)

AF:

0.206

AC:

10949

AN:

53112

Middle Eastern (MID)

AF:

0.146

AC:

838

AN:

5724

European-Non Finnish (NFE)

AF:

0.183

AC:

201060

AN:

1098354

Other (OTH)

AF:

0.216

AC:

12914

AN:

59652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

10472

20944

31415

41887

52359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7362

14724

22086

29448

36810

<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:

0.228

AC:

34611

AN:

152060

Hom.:

4338

Cov.:

AF XY:

0.233

AC XY:

17315

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.248

AC:

10271

AN:

41484

American (AMR)

AF:

0.257

AC:

3923

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

648

AN:

3472

East Asian (EAS)

AF:

0.546

AC:

2827

AN:

5174

South Asian (SAS)

AF:

0.350

AC:

1685

AN:

4812

European-Finnish (FIN)

AF:

0.204

AC:

2152

AN:

10544

Middle Eastern (MID)

AF:

0.127

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.183

AC:

12431

AN:

67996

Other (OTH)

AF:

0.212

AC:

445

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1299

2598

3896

5195

6494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.198

Hom.:

2554

Bravo

AF:

0.236

TwinsUK

AF:

0.188

AC:

698

ALSPAC

AF:

0.184

AC:

709

ESP6500AA

AF:

0.244

AC:

875

ESP6500EA

AF:

0.181

AC:

1471

ExAC

AF:

0.248

AC:

29948

Asia WGS

AF:

0.412

AC:

1431

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.3

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0060

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.047

MetaRNN

Benign

0.00012

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PhyloP100

-0.11

Sift4G

Uncertain

0.053

Polyphen

0.015

Vest4

0.019

MutPred

0.062

Gain of phosphorylation at T151 (P = 0.0969);

ClinPred

0.0017

GERP RS

1.9

Varity_R

0.036

gMVP

0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over