Variant 10-11462529-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014688.5(USP6NL):c.2399C>T(p.Ser800Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,708 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 1 hom. )

Consequence

USP6NL
NM_014688.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

Variant links:

Genes affected

USP6NL (HGNC:16858): (USP6 N-terminal like) Enables GTPase activator activity and small GTPase binding activity. Involved in several processes, including plasma membrane to endosome transport; positive regulation of GTPase activity; and retrograde transport, plasma membrane to Golgi. Located in cytoplasmic vesicle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

USP6NL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27293336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP6NL	NM_014688.5 link	c.2399C>T	p.Ser800Phe	missense_variant	15/15	ENST00000609104.6	NP_055503.1	Q92738-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
USP6NL	ENST00000609104.6 link	c.2399C>T	p.Ser800Phe	missense_variant	15/15	1	NM_014688.5	ENSP00000476462.1	Q92738-1
USP6NL	ENST00000379237.6 link	c.2468C>T	p.Ser823Phe	missense_variant	14/14	5		ENSP00000368539.2	X6RAB3
USP6NL	ENST00000277575.5 link	c.2450C>T	p.Ser817Phe	missense_variant	14/14	5		ENSP00000277575.5	Q92738-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.2450C>T (p.S817F) alteration is located in exon 14 (coding exon 14) of the USP6NL gene. This alteration results from a C to T substitution at nucleotide position 2450, causing the serine (S) at amino acid position 817 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

T;.;.

Eigen

Benign

-0.0015

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.0055

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.95

.;N;.

REVEL

Benign

0.20

Sift

Pathogenic

0.0

.;D;.

Sift4G

Uncertain

0.059

T;T;T

Polyphen

0.47

P;P;.

Vest4

0.14

MutPred

0.28

Loss of glycosylation at S800 (P = 1e-04);.;.;

MVP

0.64

MPC

0.29

ClinPred

0.44

GERP RS

6.0

Varity_R

0.16

gMVP

0.15

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over