chr10-11462602-C-T

Variant names:

• chr10-11462602-C-T
• NM_014688.5:c.2326G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014688.5(USP6NL):​c.2326G>A​(p.Gly776Ser) 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. 16/22 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)
• Consequence: USP6NL NM_014688.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.538
• Publications: 0 publications found

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]

ENSG00000301463 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03615153).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014688.5. 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
	USP6NL	NM_014688.5	MANE Select	c.2326G>A	p.Gly776Ser	missense	Exon 15 of 15	NP_055503.1	Q92738-1
	USP6NL	NM_001391959.1		c.2395G>A	p.Gly799Ser	missense	Exon 14 of 14	NP_001378888.1	X6RAB3
	USP6NL	NM_001080491.5		c.2377G>A	p.Gly793Ser	missense	Exon 14 of 14	NP_001073960.1	Q92738-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP6NL	ENST00000609104.6	TSL:1 MANE Select	c.2326G>A	p.Gly776Ser	missense	Exon 15 of 15	ENSP00000476462.1	Q92738-1
	USP6NL	ENST00000938640.1		c.2446G>A	p.Gly816Ser	missense	Exon 17 of 17	ENSP00000608699.1
	USP6NL	ENST00000938639.1		c.2404G>A	p.Gly802Ser	missense	Exon 16 of 16	ENSP00000608698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.018
DANN	Benign	0.45
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.44	N
PhyloP100		-0.54
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.021
Sift	Benign	0.66	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.023
MutPred		0.11		Loss of catalytic residue at G776 (P = 0.0274)
MVP		0.20
MPC		0.12
ClinPred		0.022	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.016
gMVP		0.086
Mutation Taster		=98/2	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

hg19: chr10-11504601;