10-11463246-C-T

Position:

• chr10-11463246-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014688.5(USP6NL):​c.1682G>A​(p.Ser561Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP6NL NM_014688.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.298

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02592808).
• BP6: Variant 10-11463246-C-T is Benign according to our data. Variant chr10-11463246-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2258596.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP6NL	NM_014688.5	c.1682G>A	p.Ser561Asn	missense_variant	15/15	ENST00000609104.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP6NL	ENST00000609104.6	c.1682G>A	p.Ser561Asn	missense_variant	15/15	1	NM_014688.5	P1
USP6NL	ENST00000379237.6	c.1751G>A	p.Ser584Asn	missense_variant	14/14	5
USP6NL	ENST00000277575.5	c.1733G>A	p.Ser578Asn	missense_variant	14/14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.086
DANN	Benign	0.15
DEOGEN2	Benign	0.055	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.026	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.4	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.018
MutPred		0.16		Loss of glycosylation at S561 (P = 0.0071);.;.;
MVP		0.24
MPC		0.11
ClinPred		0.036	T
GERP RS		-0.35
Varity_R		0.020
gMVP		0.059

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-11505245;