Variant 17-78164260-C-G 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_001163075.2(C17orf99):c.536C>G(p.Pro179Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,551,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

C17orf99
NM_001163075.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

C17orf99 (HGNC:34490): (chromosome 17 open reading frame 99) Predicted to enable transmembrane signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway; mature B cell differentiation involved in immune response; and positive regulation of immunoglobulin production in mucosal tissue. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

C17orf99 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=0.034231335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C17orf99	NM_001163075.2 linkuse as main transcript	c.536C>G	p.Pro179Arg	missense_variant	4/5	ENST00000340363.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C17orf99	ENST00000340363.10 linkuse as main transcript	c.536C>G	p.Pro179Arg	missense_variant	4/5	1	NM_001163075.2	P1
C17orf99	ENST00000591995.1 linkuse as main transcript	c.524C>G	p.Pro175Arg	missense_variant	3/3	4
C17orf99	ENST00000586029.1 linkuse as main transcript	c.345C>G	p.Ala115=	synonymous_variant	2/3	3
C17orf99	ENST00000451352.3 linkuse as main transcript	n.509C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152262

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:

0.00173

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

GnomAD3 exomes

AF:

0.000148

AC:

AN:

155240

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

82402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00202

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1399134

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

690084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000532

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

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

Aug 30, 2021

The c.536C>G (p.P179R) alteration is located in exon 4 (coding exon 4) of the C17orf99 gene. This alteration results from a C to G substitution at nucleotide position 536, causing the proline (P) at amino acid position 179 to be replaced by an arginine (R). 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

0.16

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-4.7

D;.

REVEL

Benign

0.044

Sift

Uncertain

0.029

D;.

Sift4G

Uncertain

0.033

D;D

Polyphen

0.66

P;.

Vest4

0.27

MutPred

0.45

Gain of methylation at P179 (P = 0.0273);.;

MVP

0.18

ClinPred

0.12

GERP RS

3.3

Varity_R

0.18

gMVP

0.42

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