8-12138295-C-A

Variant names:

• chr8-12138295-C-A
• rs201369910
• NM_201402.3:c.466G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_201402.3(USP17L2):​c.466G>T​(p.Gly156Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000485 in 1,475,564 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00048 (8 hom.)
• Consequence: USP17L2 NM_201402.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08
• Publications: 1 publications found

Genes affected

USP17L2 (HGNC:34434): (ubiquitin specific peptidase 17 like family member 2) DUB3 is a member of the ubiquitin processing protease (UBP) subfamily of deubiquitinating enzymes. See USP1 (MIM 603478) for background information.[supplied by OMIM, Mar 2008]

FAM66D (HGNC:24159): (family with sequence similarity 66 member D)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012592852).
• BP6: Variant 8-12138295-C-A is Benign according to our data. Variant chr8-12138295-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2658427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201402.3. 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
	USP17L2	NM_201402.3	MANE Select	c.466G>T	p.Gly156Cys	missense	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-7128C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L2	ENST00000333796.4	TSL:6 MANE Select	c.466G>T	p.Gly156Cys	missense	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
	FAM66D	ENST00000434078.3	TSL:5	n.545-7344C>A		intron	N/A
	FAM66D	ENST00000653269.1		n.706-7128C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 71 AN: 140390 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0000800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000728

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000695

Gnomad OTH AF: 0.00105

GnomAD2 exomes AF: 0.000585 AC: 120 AN: 204956 AF XY: 0.000572

Gnomad AFR exome AF: 0.0000877

Gnomad AMR exome AF: 0.000910

Gnomad ASJ exome AF: 0.000657

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000702

Gnomad NFE exome AF: 0.000742

Gnomad OTH exome AF: 0.000751

GnomAD4 exome AF: 0.000482 AC: 644 AN: 1335080 Hom.: 8 Cov.: 32 AF XY: 0.000483 AC XY: 322 AN XY: 666278

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

African (AFR) AF: 0.0000330 AC: 1 AN: 30308

American (AMR) AF: 0.000859 AC: 36 AN: 41930

Ashkenazi Jewish (ASJ) AF: 0.000323 AC: 8 AN: 24738

East Asian (EAS) AF: 0.00 AC: 0 AN: 34250

South Asian (SAS) AF: 0.00 AC: 0 AN: 76290

European-Finnish (FIN) AF: 0.000663 AC: 33 AN: 49754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3680

European-Non Finnish (NFE) AF: 0.000537 AC: 547 AN: 1019048

Other (OTH) AF: 0.000345 AC: 19 AN: 55082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000505 AC: 71 AN: 140484 Hom.: 3 Cov.: 31 AF XY: 0.000469 AC XY: 32 AN XY: 68204

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

African (AFR) AF: 0.0000798 AC: 3 AN: 37586

American (AMR) AF: 0.000727 AC: 10 AN: 13760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3336

East Asian (EAS) AF: 0.00 AC: 0 AN: 4304

South Asian (SAS) AF: 0.00 AC: 0 AN: 3980

European-Finnish (FIN) AF: 0.00112 AC: 11 AN: 9778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.000695 AC: 45 AN: 64706

Other (OTH) AF: 0.00104 AC: 2 AN: 1930

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000321 Hom.: 1

ExAC AF: 0.000535 AC: 58

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.12
Sift	Benign	0.043	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.18
MVP		0.24
MPC		1.1
ClinPred		0.088	T
GERP RS		-1.5
Varity_R		0.18
gMVP		0.025
Mutation Taster		=100/0	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: rs201369910; hg19: chr8-11995804;