rs551142835

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-12138226-C-G
• chr8-12138226-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_201402.3(USP17L2):​c.535G>C​(p.Gly179Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000094 in 138,300 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 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. G179S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000094 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP17L2 NM_201402.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12423211).

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>C	p.Gly179Arg	missense	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-7197C>G		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>C	p.Gly179Arg	missense	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
	FAM66D	ENST00000434078.3	TSL:5	n.545-7413C>G		intron	N/A
	FAM66D	ENST00000653269.1		n.706-7197C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000940 AC: 13 AN: 138300 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000203

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 3 AN: 62942 AF XY: 0.0000630

Gnomad AFR exome AF: 0.00

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: 0.0000789

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000142 AC: 162 AN: 1138452 Hom.: 0 Cov.: 21 AF XY: 0.000142 AC XY: 82 AN XY: 575554

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

African (AFR) AF: 0.0000753 AC: 2 AN: 26560

American (AMR) AF: 0.0000252 AC: 1 AN: 39718

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 32632

South Asian (SAS) AF: 0.00 AC: 0 AN: 70886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43480

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

European-Non Finnish (NFE) AF: 0.000173 AC: 147 AN: 849948

Other (OTH) AF: 0.000248 AC: 12 AN: 48454

⚠️ 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: 0.0000940 AC: 13 AN: 138300 Hom.: 1 Cov.: 31 AF XY: 0.0000747 AC XY: 5 AN XY: 66976

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

African (AFR) AF: 0.00 AC: 0 AN: 36702

American (AMR) AF: 0.00 AC: 0 AN: 13568

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4176

South Asian (SAS) AF: 0.00 AC: 0 AN: 3826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000203 AC: 13 AN: 64126

Other (OTH) AF: 0.00 AC: 0 AN: 1882

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000222045), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.17
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.076
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.031	D
Polyphen		0.44	B
Vest4		0.092
MutPred		0.46		Loss of ubiquitination at K181 (P = 0.0116)
MVP		0.21
MPC		0.71
ClinPred		0.18	T
GERP RS		-1.5
Varity_R		0.18
gMVP		0.0092
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;