17-32341240-C-T

Variant names:

Variant summary

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

The NM_022344.4(C17orf75):c.185G>A(p.Gly62Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000874 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

C17orf75
NM_022344.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

Variant links:

Genes affected

C17orf75 (HGNC:30173): (chromosome 17 open reading frame 75) Involved in intracellular protein transport and vesicle tethering to Golgi. Located in cytoplasmic vesicle and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

C17orf75 links:

ENSG00000265794 (HGNC:):

ENSG00000265794 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=0.009317994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C17orf75	NM_022344.4 link	c.185G>A	p.Gly62Asp	missense_variant	Exon 2 of 10	ENST00000577809.6	NP_071739.2	Q9HAS0
C17orf75	XM_005258022.5 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 3 of 11		XP_005258079.1
C17orf75	XM_017024940.3 link	c.-353G>A		5_prime_UTR_variant	Exon 2 of 10		XP_016880429.1
C17orf75	XM_017024941.3 link	c.-353G>A		5_prime_UTR_variant	Exon 2 of 10		XP_016880430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C17orf75	ENST00000577809.6 link	c.185G>A	p.Gly62Asp	missense_variant	Exon 2 of 10	1	NM_022344.4	ENSP00000464275.1	Q9HAS0
C17orf75	ENST00000583774.5 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 3 of 9	5		ENSP00000462127.1	J3KRR1
C17orf75	ENST00000580558.5 link	c.-353G>A		5_prime_UTR_variant	Exon 2 of 9	5		ENSP00000464759.1	K7EII1
C17orf75	ENST00000583334.5 link	c.-377G>A		5_prime_UTR_variant	Exon 2 of 6	3		ENSP00000468451.1	K7ERX0
C17orf75	ENST00000583221.5 link	n.185G>A		non_coding_transcript_exon_variant	Exon 2 of 7	5		ENSP00000463184.1	J3QKQ1

Frequencies

GnomAD3 genomes

AF:

0.000546

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000128

AC:

AN:

249258

Hom.:

AF XY:

0.0000961

AC XY:

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.00187

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1461668

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000539

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000953

Hom.:

Bravo

AF:

0.000737

ESP6500AA

AF:

0.00151

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.185G>A (p.G62D) alteration is located in exon 2 (coding exon 2) of the C17orf75 gene. This alteration results from a G to A substitution at nucleotide position 185, causing the glycine (G) at amino acid position 62 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

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.019

.;T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0093

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

.;M;.

PROVEAN

Benign

-1.3

N;.;.

REVEL

Benign

0.045

Sift

Benign

0.061

T;.;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.45

.;B;.

Vest4

0.29

MVP

0.068

MPC

0.30

ClinPred

0.018

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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