Variant 17-73236243-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001351264.2(C17orf80):c.761G>A(p.Gly254Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

C17orf80
NM_001351264.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.396

Variant links:

Genes affected

C17orf80 (HGNC:29601): (mitochondrial nucleoid associated protein 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

C17orf80 links:

FAM104A (HGNC:25918): (VCP nuclear cofactor family member 1)

FAM104A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011971027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C17orf80	NM_001351264.2 linkuse as main transcript	c.761G>A	p.Gly254Asp	missense_variant	3/6	ENST00000535032.7	NP_001338193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C17orf80	ENST00000535032.7 linkuse as main transcript	c.761G>A	p.Gly254Asp	missense_variant	3/6	1	NM_001351264.2	ENSP00000440551	A2	Q9BSJ5-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000112

AC:

AN:

251106

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000643

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000118

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.761G>A (p.G254D) alteration is located in exon 3 (coding exon 1) of the C17orf80 gene. This alteration results from a G to A substitution at nucleotide position 761, causing the glycine (G) at amino acid position 254 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.6

DANN

Benign

0.87

DEOGEN2

Benign

0.0067

T;.;T;.;.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.83

T;.;T;T;T;.

M_CAP

Benign

0.039

MetaRNN

Benign

0.012

T;T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.69

.;N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PROVEAN

Benign

-0.59

N;.;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.76

T;.;T;T;T;T

Sift4G

Benign

0.38

T;T;T;T;T;T

Polyphen

0.049, 0.21, 0.062

.;B;B;B;B;B

Vest4

0.049

MutPred

0.078

Loss of MoRF binding (P = 0.0495);Loss of MoRF binding (P = 0.0495);Loss of MoRF binding (P = 0.0495);Loss of MoRF binding (P = 0.0495);Loss of MoRF binding (P = 0.0495);Loss of MoRF binding (P = 0.0495);

MVP

0.24

MPC

0.24

ClinPred

0.048

GERP RS

1.8

Varity_R

0.023

gMVP

0.026

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