dbSNP rs1714987: C17orf78:p.Thr152Ser (chr17-37386072-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.251

AC:

60489

AN:

241222

Hom.:

9058

AF XY:

0.248

AC XY:

32383

AN XY:

130696

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 SAS exome

AF:

0.327

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

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.315

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.552

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.228

AC:

34611

AN:

152060

Hom.:

4338

Cov.:

AF XY:

0.233

AC XY:

17315

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.546

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.183

Gnomad4 OTH

AF:

0.212

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over