rs35029887

Positions:

chr1-108922543-ACTT-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_013296.5(GPSM2):c.1572_1574delTTC(p.Ser525del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,607,800 control chromosomes in the GnomAD database, including 72,591 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11187 hom., cov: 0)

Exomes 𝑓: 0.28 ( 61404 hom. )

Consequence

GPSM2
NM_013296.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

GPSM2 (HGNC:29501): (G protein signaling modulator 2) The protein encoded by this gene belongs to a family of proteins that modulate activation of G proteins, which transduce extracellular signals received by cell surface receptors into integrated cellular responses. The N-terminal half of this protein contains 10 copies of leu-gly-asn (LGN) repeat, and the C-terminal half contains 4 GoLoco motifs, which are involved in guanine nucleotide exchange. This protein may play a role in neuroblast division and in the development of normal hearing. Mutations in this gene are associated with autosomal recessive nonsyndromic deafness (DFNB82). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

GPSM2 links:

CLCC1 (HGNC:29675): (chloride channel CLIC like 1) Predicted to enable chloride channel activity. Predicted to be involved in chloride transport. Located in endoplasmic reticulum and mitochondria-associated endoplasmic reticulum membrane. Implicated in retinitis pigmentosa 32. [provided by Alliance of Genome Resources, Apr 2022]

CLCC1 links:

AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

AKNAD1 links:

GPSM2 (HGNC:):

GPSM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_013296.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 1-108922543-ACTT-A is Benign according to our data. Variant chr1-108922543-ACTT-A is described in ClinVar as [Likely_benign]. Clinvar id is 226649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPSM2	NM_013296.5 linkuse as main transcript	c.1572_1574delTTC	p.Ser525del	disruptive_inframe_deletion	13/15	ENST00000264126.9	NP_037428.3	P81274A0A024R0F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPSM2	ENST00000264126.9 linkuse as main transcript	c.1572_1574delTTC	p.Ser525del	disruptive_inframe_deletion	13/15	1	NM_013296.5	ENSP00000264126.3		P81274

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

53959

AN:

151478

Hom.:

11154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.0541

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.315

GnomAD3 exomes

AF:

0.283

AC:

71035

AN:

251372

Hom.:

11396

AF XY:

0.280

AC XY:

38021

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.577

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.0575

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.282

AC:

410970

AN:

1456204

Hom.:

61404

AF XY:

0.282

AC XY:

204431

AN XY:

724626

show subpopulations

Gnomad4 AFR exome

AF:

0.577

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.0560

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.357

AC:

54050

AN:

151596

Hom.:

11187

Cov.:

AF XY:

0.351

AC XY:

26030

AN XY:

74088

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.0541

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.290

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.332

Hom.:

1621

Bravo

AF:

0.360

Asia WGS

AF:

0.208

AC:

726

AN:

3478

EpiCase

AF:

0.293

EpiControl

AF:

0.283

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 31, 2014	Ser525del in exon 13 of GPSM2: This variant is a deletion of 1 amino acid at pos ition 525 and is not predicted to alter the protein reading-frame or impact the protein. It has been identified in in 28% (2331/8254) of European American chrom osomes and 56% (2409/4266) of African American chromosomes by the NHLBI Exome Se quencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs35029887). -

Chudley-McCullough syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Hearing loss, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over