rs4445554

chr10-11522422-C-T

Variant summary

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

The NM_014688.5(USP6NL):c.155+2964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,052 control chromosomes in the GnomAD database, including 4,430 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 0.23 (4430 hom., cov: 33)
• Consequence: USP6NL NM_014688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP6NL	NM_014688.5	c.155+2964G>A		intron_variant		ENST00000609104.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP6NL	ENST00000609104.6	c.155+2964G>A		intron_variant		1	NM_014688.5	P1
USP6NL	ENST00000277575.5	c.206+2964G>A		intron_variant		5
USP6NL	ENST00000379237.6	c.224+2964G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34180 AN: 151934 Hom.: 4418 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.225 AC: 34219 AN: 152052 Hom.: 4430 Cov.: 33 AF XY: 0.232 AC XY: 17214 AN XY: 74316

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.208

Alfa AF: 0.199 Hom.: 4019

Bravo AF: 0.227

Asia WGS AF: 0.376 AC: 1302 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.40
Dann	Benign	0.74

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: rs4445554; hg19: chr10-11564421;