rs1714987

Variant names:

• chr17-37386072-C-G
• rs1714987
• NM_173625.5:c.455C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 31 publications found

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]

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173625.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf78	NM_173625.5	MANE Select	c.455C>G	p.Thr152Ser	missense	Exon 4 of 7	NP_775896.3
	ACACA	NM_198834.3	MANE Select	c.38+20190G>C		intron	N/A	NP_942131.1
	ACACA	NM_198839.3		c.-747-16585G>C		intron	N/A	NP_942136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf78	ENST00000615133.2	TSL:1 MANE Select	c.455C>G	p.Thr152Ser	missense	Exon 4 of 7	ENSP00000478886.1
	ACACA	ENST00000616317.5	TSL:1 MANE Select	c.38+20190G>C		intron	N/A	ENSP00000483300.1
	C17orf78	ENST00000611038.4	TSL:2	c.392-3174C>G		intron	N/A	ENSP00000477816.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34578 AN: 151942 Hom.: 4324 Cov.: 32

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

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.: 31 AF XY: 0.212 AC XY: 152095 AN XY: 717682

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

GnomAD4 genome AF: 0.228 AC: 34611 AN: 152060 Hom.: 4338 Cov.: 32 AF XY: 0.233 AC XY: 17315 AN XY: 74324

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: 37 AN: 292

European-Non Finnish (NFE) AF: 0.183 AC: 12431 AN: 67996

Other (OTH) AF: 0.212 AC: 445 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.3
DANN	Benign	0.95
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.047	N
MetaRNN	Benign	0.00012	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.11
Sift4G	Uncertain	0.053	T
Polyphen		0.015	B
Vest4		0.019
MutPred		0.062		Gain of phosphorylation at T151 (P = 0.0969)
ClinPred		0.0017	T
GERP RS		1.9
Varity_R		0.036
gMVP		0.086
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1714987; hg19: chr17-35743010;