NM_014688.5:c.5-9980C>T

Variant names:

• chr10-11537547-G-A
• rs10508425
• NM_014688.5:c.5-9980C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014688.5(USP6NL):​c.5-9980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,986 control chromosomes in the GnomAD database, including 4,661 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 (4661 hom., cov: 32)
• Consequence: USP6NL NM_014688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• 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 rank	MANE	Protein	UniProt
USP6NL	NM_014688.5	c.5-9980C>T		intron_variant	Intron 2 of 14	ENST00000609104.6	NP_055503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP6NL	ENST00000609104.6	c.5-9980C>T		intron_variant	Intron 2 of 14	1	NM_014688.5	ENSP00000476462.1
USP6NL	ENST00000379237.6	c.74-9980C>T		intron_variant	Intron 1 of 13	5		ENSP00000368539.2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35331 AN: 151868 Hom.: 4647 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.233 AC: 35374 AN: 151986 Hom.: 4661 Cov.: 32 AF XY: 0.239 AC XY: 17742 AN XY: 74296

African (AFR) AF: 0.207 AC: 8588 AN: 41448

American (AMR) AF: 0.293 AC: 4483 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3027 AN: 5172

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4810

European-Finnish (FIN) AF: 0.246 AC: 2594 AN: 10524

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.210 AC: 14260 AN: 67964

Other (OTH) AF: 0.216 AC: 456 AN: 2112

Alfa AF: 0.213 Hom.: 918

Bravo AF: 0.235

Asia WGS AF: 0.383 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.89
DANN	Benign	0.20
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10508425; hg19: chr10-11579546;