8-12138226-C-T

Variant names:

• chr8-12138226-C-T
• rs551142835
• NM_201402.3:c.535G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_201402.3(USP17L2):​c.535G>A​(p.Gly179Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00046 (16 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP17L2 NM_201402.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.173
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026968181).
• BP6: Variant 8-12138226-C-T is Benign according to our data. Variant chr8-12138226-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3025402.Status of the report is criteria_provided_single_submitter, 1 stars.

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.535G>A	p.Gly179Ser	missense	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-7197C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L2	ENST00000333796.4	TSL:6 MANE Select	c.535G>A	p.Gly179Ser	missense	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
	FAM66D	ENST00000434078.3	TSL:5	n.545-7413C>T		intron	N/A
	FAM66D	ENST00000653269.1		n.706-7197C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000463 AC: 64 AN: 138272 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000791

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000523

Gnomad FIN AF: 0.000417

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000421

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000222 AC: 14 AN: 62942 AF XY: 0.000284

Gnomad AFR exome AF: 0.000596

Gnomad AMR exome AF: 0.0000785

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000395

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000459 AC: 522 AN: 1138380 Hom.: 16 Cov.: 21 AF XY: 0.000412 AC XY: 237 AN XY: 575516

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

African (AFR) AF: 0.000791 AC: 21 AN: 26544

American (AMR) AF: 0.000101 AC: 4 AN: 39718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23484

East Asian (EAS) AF: 0.0000306 AC: 1 AN: 32632

South Asian (SAS) AF: 0.000212 AC: 15 AN: 70884

European-Finnish (FIN) AF: 0.0000460 AC: 2 AN: 43476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3290

European-Non Finnish (NFE) AF: 0.000527 AC: 448 AN: 849904

Other (OTH) AF: 0.000640 AC: 31 AN: 48448

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000463 AC: 64 AN: 138372 Hom.: 2 Cov.: 31 AF XY: 0.000522 AC XY: 35 AN XY: 67072

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

African (AFR) AF: 0.000788 AC: 29 AN: 36780

American (AMR) AF: 0.000147 AC: 2 AN: 13586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3322

East Asian (EAS) AF: 0.00 AC: 0 AN: 4166

South Asian (SAS) AF: 0.000524 AC: 2 AN: 3820

European-Finnish (FIN) AF: 0.000417 AC: 4 AN: 9586

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

European-Non Finnish (NFE) AF: 0.000421 AC: 27 AN: 64120

Other (OTH) AF: 0.00 AC: 0 AN: 1900

⚠️ 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: 0.00 Hom.: 0

ExAC AF: 0.000120 AC: 3

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	0.091
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.9
DANN	Benign	0.87
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.17
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.052
Sift	Benign	0.23	T
Sift4G	Benign	0.21	T
Polyphen		0.64	P
Vest4		0.060
MutPred		0.38		Gain of disorder (P = 0.0803)
MVP		0.12
MPC		1.1
ClinPred		0.052	T
GERP RS		-1.5
Varity_R		0.071
gMVP		0.0099
Mutation Taster		=97/3	polymorphism

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: rs551142835; hg19: chr8-11995735;