rs7085769

Positions:

• chr10-11501662-G-A
• chr10-11501662-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014688.5(USP6NL):​c.277-454C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,022 control chromosomes in the GnomAD database, including 4,359 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4359 hom., cov: 32)
• Consequence: USP6NL NM_014688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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]

LOC105376410 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP6NL	NM_014688.5	c.277-454C>T		intron_variant		ENST00000609104.6	NP_055503.1
LOC105376410	XR_007062053.1	n.151+2820G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP6NL	ENST00000609104.6	c.277-454C>T		intron_variant		1	NM_014688.5	ENSP00000476462	P1
USP6NL	ENST00000277575.5	c.328-454C>T		intron_variant		5		ENSP00000277575
USP6NL	ENST00000379237.6	c.346-454C>T		intron_variant		5		ENSP00000368539

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33774 AN: 151904 Hom.: 4345 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33815 AN: 152022 Hom.: 4359 Cov.: 32 AF XY: 0.229 AC XY: 17007 AN XY: 74300

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.207

Alfa AF: 0.206 Hom.: 6985

Bravo AF: 0.224

Asia WGS AF: 0.379 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs7085769; hg19: chr10-11543661;