4-9253444-T-G

Variant names:

• chr4-9253444-T-G
• rs763198779
• NM_001256860.1:c.67T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001256860.1(USP17L19):​c.67T>G​(p.Ser23Ala) 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. 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. S23P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP17L19 NM_001256860.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533
• Publications: 1 publications found

Genes affected

USP17L19 (HGNC:44447): (ubiquitin specific peptidase 17 like family member 19) Predicted to enable cysteine-type endopeptidase activity and thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination and regulation of apoptotic process. Predicted to be located in endoplasmic reticulum. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288075 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.005769849).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256860.1. 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
	USP17L19	NM_001256860.1	MANE Select	c.67T>G	p.Ser23Ala	missense	Exon 1 of 1	NP_001243789.1	D6RCP7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L19	ENST00000515566.1	TSL:6 MANE Select	c.67T>G	p.Ser23Ala	missense	Exon 1 of 1	ENSP00000425582.1	D6RCP7
	ENSG00000288075	ENST00000658713.1		n.487-49955A>C		intron	N/A
	ENSG00000288075	ENST00000666840.2		n.643+121643A>C		intron	N/A

Frequencies

GnomAD3 genomes AC: 0 AN: 0 Hom.: 0 Cov.: 0

GnomAD2 exomes AF: 0.0311 AC: 34 AN: 1094 AF XY: 0.0309

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00112 AC: 3 AN: 2670 Hom.: 0 Cov.: 0 AF XY: 0.00121 AC XY: 2 AN XY: 1656

African (AFR) AF: 0.00 AC: 0 AN: 170

American (AMR) AF: 0.00439 AC: 1 AN: 228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00758 AC: 2 AN: 264

South Asian (SAS) AF: 0.00 AC: 0 AN: 1220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 648

Other (OTH) AF: 0.00 AC: 0 AN: 112

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.0
DANN	Benign	0.75
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.53
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.045
Sift	Benign	0.93	T
Sift4G	Benign	0.54	T
Vest4		0.11
MutPred		0.26		Loss of phosphorylation at S23 (P = 0.0353)
ClinPred		0.0059	T
GERP RS		0.37
PromoterAI		0.0080	Neutral
Varity_R		0.069
gMVP		0.033
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: rs763198779; hg19: chr4-9255170;