rs14170

Variant names:

• chr2-61188357-A-G
• rs14170
• NM_014709.4:c.10386T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-61188357-A-G
• chr2-61188357-A-C
• chr2-61188357-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014709.4(USP34):​c.10386T>C​(p.Ala3462Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,613,356 control chromosomes in the GnomAD database, including 177,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17238 hom., cov: 32)
  • Exomes 𝑓: 0.46 (160346 hom.)
• Consequence: USP34 NM_014709.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.341
• Publications: 23 publications found

Genes affected

USP34 (HGNC:20066): (ubiquitin specific peptidase 34) Enables cysteine-type endopeptidase activity and thiol-dependent deubiquitinase. Involved in positive regulation of canonical Wnt signaling pathway and protein K48-linked deubiquitination. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

AHSA2P (HGNC:):

AHSA2P (HGNC:20437): (activator of HSP90 ATPase homolog 2, pseudogene) Predicted to enable ATPase activator activity. Predicted to be involved in positive regulation of ATPase activity and protein folding. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-61188357-A-G is Benign according to our data. Variant chr2-61188357-A-G is described in ClinVar as Benign. ClinVar VariationId is 1229915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.341 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014709.4. 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
	USP34	NM_014709.4	MANE Select	c.10386T>C	p.Ala3462Ala	synonymous	Exon 80 of 80	NP_055524.3
	AHSA2P	NR_152210.1		n.2547A>G		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP34	ENST00000398571.7	TSL:5 MANE Select	c.10386T>C	p.Ala3462Ala	synonymous	Exon 80 of 80	ENSP00000381577.2	Q70CQ2-1
	AHSA2P	ENST00000394457.7	TSL:1	n.3728A>G		non_coding_transcript_exon	Exon 6 of 6
	USP34	ENST00000411912.5	TSL:5	c.3414T>C	p.Ala1138Ala	synonymous	Exon 26 of 26	ENSP00000398960.1	H7C183

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71644 AN: 151870 Hom.: 17213 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.483

GnomAD2 exomes AF: 0.441 AC: 110120 AN: 249468 AF XY: 0.437

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.497

Gnomad EAS exome AF: 0.373

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.486

Gnomad OTH exome AF: 0.471

GnomAD4 exome AF: 0.463 AC: 676756 AN: 1461368 Hom.: 160346 Cov.: 69 AF XY: 0.458 AC XY: 333222 AN XY: 727004

African (AFR) AF: 0.494 AC: 16518 AN: 33458

American (AMR) AF: 0.355 AC: 15868 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 13154 AN: 26136

East Asian (EAS) AF: 0.358 AC: 14211 AN: 39684

South Asian (SAS) AF: 0.270 AC: 23289 AN: 86230

European-Finnish (FIN) AF: 0.581 AC: 31012 AN: 53402

Middle Eastern (MID) AF: 0.529 AC: 2868 AN: 5418

European-Non Finnish (NFE) AF: 0.478 AC: 531731 AN: 1111978

Other (OTH) AF: 0.466 AC: 28105 AN: 60340

GnomAD4 genome AF: 0.472 AC: 71716 AN: 151988 Hom.: 17238 Cov.: 32 AF XY: 0.474 AC XY: 35201 AN XY: 74290

African (AFR) AF: 0.488 AC: 20211 AN: 41416

American (AMR) AF: 0.402 AC: 6135 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1882 AN: 5162

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4818

European-Finnish (FIN) AF: 0.600 AC: 6334 AN: 10564

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32498 AN: 67966

Other (OTH) AF: 0.481 AC: 1015 AN: 2108

Alfa AF: 0.462 Hom.: 6908

Bravo AF: 0.460

Asia WGS AF: 0.318 AC: 1109 AN: 3478

EpiCase AF: 0.482

EpiControl AF: 0.487

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.76
PhyloP100		-0.34
Mutation Taster		=99/1	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: rs14170; hg19: chr2-61415492; COSMIC: COSV100815945; COSMIC: COSV100815945;