17-32341240-C-T

Variant names:

• chr17-32341240-C-T
• rs202086475
• NM_022344.4:c.185G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 14/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 2 publications found

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]

ENSG00000265794 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009317994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022344.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf75	NM_022344.4	MANE Select	c.185G>A	p.Gly62Asp	missense	Exon 2 of 10	NP_071739.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf75	ENST00000577809.6	TSL:1 MANE Select	c.185G>A	p.Gly62Asp	missense	Exon 2 of 10	ENSP00000464275.1	Q9HAS0
	C17orf75	ENST00000583774.5	TSL:5	c.161G>A	p.Gly54Asp	missense	Exon 3 of 9	ENSP00000462127.1	J3KRR1
	C17orf75	ENST00000580558.5	TSL:5	c.-353G>A		5_prime_UTR	Exon 2 of 9	ENSP00000464759.1	K7EII1

Frequencies

GnomAD3 genomes AF: 0.000546 AC: 83 AN: 152126 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.000128 AC: 32 AN: 249258 AF XY: 0.0000961

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000404 AC: 59 AN: 1461668 Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28 AN XY: 727124

African (AFR) AF: 0.00134 AC: 45 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111860

Other (OTH) AF: 0.000166 AC: 10 AN: 60374

GnomAD4 genome AF: 0.000539 AC: 82 AN: 152244 Hom.: 0 Cov.: 31 AF XY: 0.000511 AC XY: 38 AN XY: 74432

African (AFR) AF: 0.00183 AC: 76 AN: 41548

American (AMR) AF: 0.000327 AC: 5 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000220 Hom.: 0

Bravo AF: 0.000737

ESP6500AA AF: 0.00151 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000132 AC: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.1
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.045
Sift	Benign	0.061	T
Sift4G	Benign	0.11	T
Polyphen		0.45	B
Vest4		0.29
MVP		0.068
MPC		0.30
ClinPred		0.018	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.12
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs202086475; hg19: chr17-30668259;