chr8-7973179-T-G

Variant names:

• chr8-7973179-T-G
• rs62641384
• NM_001256872.1:c.75A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001256872.1(USP17L8):​c.75A>C​(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P25P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.12 (3455 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP17L8 NM_001256872.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 2 publications found

Genes affected

USP17L8 (HGNC:37181): (ubiquitin specific peptidase 17 like family member 8) 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]

LOC124901865 (HGNC:):

FAM66E (HGNC:18735): (family with sequence similarity 66 member E)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-0.524 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256872.1. 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
	USP17L8	NM_001256872.1	MANE Select	c.75A>C	p.Pro25Pro	synonymous	Exon 1 of 1	NP_001243801.1	P0C7I0
	FAM66E	NR_027424.1		n.610+11883T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L8	ENST00000527080.1	TSL:6 MANE Select	c.75A>C	p.Pro25Pro	synonymous	Exon 1 of 1	ENSP00000485306.1	P0C7I0
	FAM66E	ENST00000529252.2	TSL:2	n.609+11883T>G		intron	N/A
	FAM66E	ENST00000533615.1	TSL:2	n.1154-11086T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 23614 Hom.: 0 Cov.: 0

Gnomad AFR 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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0174 AC: 403 AN: 23218 AF XY: 0.0159

Gnomad AFR exome AF: 0.00450

Gnomad AMR exome AF: 0.0461

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.00496

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.0242

Gnomad OTH exome AF: 0.0374

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.118 AC: 9505 AN: 80318 Hom.: 3455 Cov.: 0 AF XY: 0.143 AC XY: 6048 AN XY: 42166

African (AFR) AF: 0.0413 AC: 808 AN: 19570

American (AMR) AF: 0.214 AC: 1087 AN: 5070

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 184 AN: 912

East Asian (EAS) AF: 0.0305 AC: 145 AN: 4758

South Asian (SAS) AF: 0.129 AC: 1491 AN: 11550

European-Finnish (FIN) AF: 0.117 AC: 229 AN: 1954

Middle Eastern (MID) AF: 0.187 AC: 70 AN: 374

European-Non Finnish (NFE) AF: 0.165 AC: 5031 AN: 30494

Other (OTH) AF: 0.0816 AC: 460 AN: 5636

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 23614 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 11032

African (AFR) AF: 0.00 AC: 0 AN: 21478

American (AMR) AF: 0.00 AC: 0 AN: 870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 168

South Asian (SAS) AF: 0.00 AC: 0 AN: 158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 680

Other (OTH) AF: 0.00 AC: 0 AN: 224

Alfa AF: 0.00590 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.7
DANN	Benign	0.31
PhyloP100		-0.52
PromoterAI		0.019	Neutral
Mutation Taster		=16/84	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs62641384; hg19: chr8-7830701; COSMIC: COSV73245023; COSMIC: COSV73245023;