rs12570211

Variant names:

• chr10-11462753-T-C
• rs12570211
• NM_014688.5:c.2175A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014688.5(USP6NL):​c.2175A>G​(p.Pro725Pro) 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
• Publications: 12 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: Benign. The variant received -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.

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.2175A>G	p.Pro725Pro	synonymous	Exon 15 of 15	NP_055503.1	Q92738-1
	USP6NL	NM_001391959.1		c.2244A>G	p.Pro748Pro	synonymous	Exon 14 of 14	NP_001378888.1	X6RAB3
	USP6NL	NM_001080491.5		c.2226A>G	p.Pro742Pro	synonymous	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.2175A>G	p.Pro725Pro	synonymous	Exon 15 of 15	ENSP00000476462.1	Q92738-1
	USP6NL	ENST00000938640.1		c.2295A>G	p.Pro765Pro	synonymous	Exon 17 of 17	ENSP00000608699.1
	USP6NL	ENST00000938639.1		c.2253A>G	p.Pro751Pro	synonymous	Exon 16 of 16	ENSP00000608698.1

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

GnomAD2 exomes AF: 0.0779 AC: 19411 AN: 249250 AF XY: 0.0858

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 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

African (AFR) AF: 0.0236 AC: 790 AN: 33480

American (AMR) AF: 0.0408 AC: 1823 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3414 AN: 26136

East Asian (EAS) AF: 0.145 AC: 5742 AN: 39700

South Asian (SAS) AF: 0.197 AC: 17017 AN: 86258

European-Finnish (FIN) AF: 0.0286 AC: 1529 AN: 53390

Middle Eastern (MID) AF: 0.123 AC: 712 AN: 5768

European-Non Finnish (NFE) AF: 0.0579 AC: 64405 AN: 1111864

Other (OTH) AF: 0.0773 AC: 4668 AN: 60374

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

African (AFR) AF: 0.0228 AC: 946 AN: 41560

American (AMR) AF: 0.0506 AC: 774 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3470

East Asian (EAS) AF: 0.134 AC: 695 AN: 5182

South Asian (SAS) AF: 0.209 AC: 1010 AN: 4824

European-Finnish (FIN) AF: 0.0285 AC: 302 AN: 10610

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3862 AN: 68006

Other (OTH) AF: 0.0704 AC: 149 AN: 2116

Alfa AF: 0.0551 Hom.: 228

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.51
DANN	Benign	0.27
PhyloP100		0.25
Mutation Taster		=98/2	polymorphism (auto)

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

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