NM_001256869.2:c.852C>T

Variant names:

• chr8-12133158-G-A
• rs562149368
• NM_001256869.2:c.852C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001256869.2(USP17L7):​c.852C>T​(p.Ser284Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000549 in 1,365,782 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000069 (2 hom., cov: 35)
  • Exomes 𝑓: 0.000055 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP17L7 NM_001256869.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-12133158-G-A is Benign according to our data. Variant chr8-12133158-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2658418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.017 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

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.852C>T	p.Ser284Ser	synonymous	Exon 1 of 1	NP_001243798.1	P0C7H9
	FAM66D	NR_027425.1		n.608+11108G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L7	ENST00000530447.5	TSL:6 MANE Select	c.852C>T	p.Ser284Ser	synonymous	Exon 1 of 1	ENSP00000485337.2	P0C7H9
	FAM66D	ENST00000434078.3	TSL:5	n.545-12481G>A		intron	N/A
	FAM66D	ENST00000653269.1		n.705+10998G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000694 AC: 10 AN: 144082 Hom.: 2 Cov.: 35

Gnomad AFR AF: 0.0000504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000502

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00704

Gnomad NFE AF: 0.0000611

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000775 AC: 18 AN: 232156 AF XY: 0.0000631

Gnomad AFR exome AF: 0.000142

Gnomad AMR exome AF: 0.0000902

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000549 AC: 75 AN: 1365782 Hom.: 5 Cov.: 38 AF XY: 0.0000544 AC XY: 37 AN XY: 680460

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

African (AFR) AF: 0.0000932 AC: 3 AN: 32206

American (AMR) AF: 0.0000695 AC: 3 AN: 43168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24958

East Asian (EAS) AF: 0.0000291 AC: 1 AN: 34336

South Asian (SAS) AF: 0.000157 AC: 12 AN: 76506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50382

Middle Eastern (MID) AF: 0.000514 AC: 2 AN: 3892

European-Non Finnish (NFE) AF: 0.0000460 AC: 48 AN: 1044008

Other (OTH) AF: 0.000107 AC: 6 AN: 56326

⚠️ 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: 0.0000693 AC: 10 AN: 144198 Hom.: 2 Cov.: 35 AF XY: 0.0000428 AC XY: 3 AN XY: 70060

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

African (AFR) AF: 0.0000503 AC: 2 AN: 39770

American (AMR) AF: 0.00 AC: 0 AN: 14164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3336

East Asian (EAS) AF: 0.00 AC: 0 AN: 4426

South Asian (SAS) AF: 0.000502 AC: 2 AN: 3982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10006

Middle Eastern (MID) AF: 0.00758 AC: 2 AN: 264

European-Non Finnish (NFE) AF: 0.0000611 AC: 4 AN: 65422

Other (OTH) AF: 0.00 AC: 0 AN: 1984

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000365663), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000253 Hom.: 0

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
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.43
PhyloP100		-0.017

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: rs562149368; hg19: chr8-11990667;