dbSNP rs202086475: C17orf75:p.Gly62Val (chr17-32341240-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022344.4(C17orf75):c.185G>T(p.Gly62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G62D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

C17orf75
NM_022344.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14639881).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C17orf75	NM_022344.4 link	c.185G>T	p.Gly62Val	missense_variant	Exon 2 of 10	ENST00000577809.6	NP_071739.2	Q9HAS0
C17orf75	XM_005258022.5 link	c.161G>T	p.Gly54Val	missense_variant	Exon 3 of 11		XP_005258079.1
C17orf75	XM_017024940.3 link	c.-353G>T		5_prime_UTR_variant	Exon 2 of 10		XP_016880429.1
C17orf75	XM_017024941.3 link	c.-353G>T		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>T	p.Gly62Val	missense_variant	Exon 2 of 10	1	NM_022344.4	ENSP00000464275.1	Q9HAS0
C17orf75	ENST00000583774.5 link	c.161G>T	p.Gly54Val	missense_variant	Exon 3 of 9	5		ENSP00000462127.1	J3KRR1
C17orf75	ENST00000580558.5 link	c.-353G>T		5_prime_UTR_variant	Exon 2 of 9	5		ENSP00000464759.1	K7EII1
C17orf75	ENST00000583334.5 link	c.-377G>T		5_prime_UTR_variant	Exon 2 of 6	3		ENSP00000468451.1	K7ERX0
C17orf75	ENST00000583221.5 link	n.185G>T		non_coding_transcript_exon_variant	Exon 2 of 7	5		ENSP00000463184.1	J3QKQ1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249258

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.083

.;T;T

Eigen

Benign

-0.011

Eigen_PC

Benign

-0.0023

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

.;M;.

PROVEAN

Uncertain

-3.1

D;.;.

REVEL

Benign

0.065

Sift

Benign

0.035

D;.;.

Sift4G

Uncertain

0.046

D;D;T

Polyphen

0.74

.;P;.

Vest4

0.25

MutPred

0.21

Loss of glycosylation at S61 (P = 0.0641);Loss of glycosylation at S61 (P = 0.0641);.;

MVP

0.068

MPC

0.41

ClinPred

0.74

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.12

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