17-32341240-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/20 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
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14639881).

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>T	p.Gly62Val	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>T	p.Gly62Val	missense	Exon 2 of 10	ENSP00000464275.1	Q9HAS0
	C17orf75	ENST00000583774.5	TSL:5	c.161G>T	p.Gly54Val	missense	Exon 3 of 9	ENSP00000462127.1	J3KRR1
	C17orf75	ENST00000580558.5	TSL:5	c.-353G>T		5_prime_UTR	Exon 2 of 9	ENSP00000464759.1	K7EII1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249258 AF XY: 0.00000740

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461668 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727124

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 0.0000116 AC: 1 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: 0.0000166 AC: 1 AN: 60374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.0023
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.1
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.065
Sift	Benign	0.035	D
Sift4G	Uncertain	0.046	D
Polyphen		0.74	P
Vest4		0.25
MutPred		0.21		Loss of glycosylation at S61 (P = 0.0641)
MVP		0.068
MPC		0.41
ClinPred		0.74	D
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

Other links and lift over

dbSNP: rs202086475; hg19: chr17-30668259;