10-11462753-T-A

Variant names:

• chr10-11462753-T-A
• NM_014688.5:c.2175A>T
• USP6NL p.Pro725Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014688.5(USP6NL):​c.2175A>T​(p.Pro725Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: USP6NL NM_014688.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.252 with no splicing effect.

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.39
DANN	Benign	0.31
PhyloP100		0.25

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-11504752;