rs12570211

Positions:

• chr10-11462753-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014688.5(USP6NL):​c.2175A>G​(p.Pro725=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 1,613,966 control chromosomes in the GnomAD database, including 5,179 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 0.054 (388 hom., cov: 32)
  • Exomes 𝑓: 0.068 (4791 hom.)
• Consequence: USP6NL NM_014688.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.252 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP6NL	NM_014688.5	c.2175A>G	p.Pro725=	synonymous_variant	15/15	ENST00000609104.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP6NL	ENST00000609104.6	c.2175A>G	p.Pro725=	synonymous_variant	15/15	1	NM_014688.5	P1
USP6NL	ENST00000379237.6	c.2244A>G	p.Pro748=	synonymous_variant	14/14	5
USP6NL	ENST00000277575.5	c.2226A>G	p.Pro742=	synonymous_variant	14/14	5

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8278 AN: 152154 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0707

GnomAD3 exomes AF: 0.0779 AC: 19411 AN: 249250 Hom.: 1168 AF XY: 0.0858 AC XY: 11596 AN XY: 135224

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.0393

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.200

Gnomad FIN exome AF: 0.0292

Gnomad NFE exome AF: 0.0598

Gnomad OTH exome AF: 0.0843

GnomAD4 exome AF: 0.0685 AC: 100100 AN: 1461694 Hom.: 4791 Cov.: 32 AF XY: 0.0727 AC XY: 52885 AN XY: 727128

Gnomad4 AFR exome AF: 0.0236

Gnomad4 AMR exome AF: 0.0408

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.0286

Gnomad4 NFE exome AF: 0.0579

Gnomad4 OTH exome AF: 0.0773

GnomAD4 genome AF: 0.0544 AC: 8281 AN: 152272 Hom.: 388 Cov.: 32 AF XY: 0.0561 AC XY: 4179 AN XY: 74450

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.0506

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0285

Gnomad4 NFE AF: 0.0568

Gnomad4 OTH AF: 0.0704

Alfa AF: 0.0567 Hom.: 149

Bravo AF: 0.0526

Asia WGS AF: 0.151 AC: 524 AN: 3478

EpiCase AF: 0.0636

EpiControl AF: 0.0674

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.51
DANN	Benign	0.27

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: rs12570211; hg19: chr10-11504752; COSMIC: COSV53209170;