8-12133865-A-T

Variant names:

• chr8-12133865-A-T
• rs748545592
• NM_001256869.2:c.145T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256869.2(USP17L7):​c.145T>A​(p.Phe49Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/11 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. F49V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 35)
• Consequence: USP17L7 NM_001256869.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

Genes affected

USP17L7 (HGNC:37180): (ubiquitin specific peptidase 17 like family member 7) 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08633444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256869.2. 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
	USP17L7	NM_001256869.2	MANE Select	c.145T>A	p.Phe49Ile	missense	Exon 1 of 1	NP_001243798.1	P0C7H9
	FAM66D	NR_027425.1		n.609-11558A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L7	ENST00000530447.5	TSL:6 MANE Select	c.145T>A	p.Phe49Ile	missense	Exon 1 of 1	ENSP00000485337.2	P0C7H9
	FAM66D	ENST00000434078.3	TSL:5	n.545-11774A>T		intron	N/A
	FAM66D	ENST00000653269.1		n.706-11558A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	3.4
DANN	Benign	0.27
DEOGEN2	Benign	0.0030	T
FATHMM_MKL	Benign	0.00059	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.086	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.1
Sift4G	Benign	0.53	T
Vest4		0.13
MVP		0.067
PromoterAI		-0.019	Neutral
Varity_R		0.069
gMVP		0.050
Mutation Taster		=100/0	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: rs748545592; hg19: chr8-11991374;