rs199964596

Positions:

chr1-108922534-TCAA-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_013296.5(GPSM2):c.1566_1568delAAC(p.Thr523del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,589,560 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 9 hom. )

Consequence

GPSM2
NM_013296.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.49

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 1-108922534-TCAA-T is Benign according to our data. Variant chr1-108922534-TCAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 517193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000786 (101/128530) while in subpopulation EAS AF= 0.0161 (83/5162). AF 95% confidence interval is 0.0133. There are 0 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPSM2	NM_013296.5 linkuse as main transcript	c.1566_1568delAAC	p.Thr523del	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.1566_1568delAAC	p.Thr523del	disruptive_inframe_deletion	13/15	1	NM_013296.5	ENSP00000264126.3		P81274

Frequencies

GnomAD3 genomes

AF:

0.000794

AC:

102

AN:

128476

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000212

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.000226

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000322

Gnomad OTH

AF:

0.00162

GnomAD3 exomes

AF:

0.00146

AC:

356

AN:

243040

Hom.:

AF XY:

0.00148

AC XY:

195

AN XY:

131718

show subpopulations

Gnomad AFR exome

AF:

0.000212

Gnomad AMR exome

AF:

0.000417

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0165

Gnomad SAS exome

AF:

0.00104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.000677

GnomAD4 exome

AF:

0.000716

AC:

1046

AN:

1461030

Hom.:

AF XY:

0.000707

AC XY:

514

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0221

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.000786

AC:

101

AN:

128530

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

AN XY:

63030

show subpopulations

Gnomad4 AFR

AF:

0.000330

Gnomad4 AMR

AF:

0.000212

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0161

Gnomad4 SAS

AF:

0.000226

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000322

Gnomad4 OTH

AF:

0.00160

Alfa

AF:

0.000261

Hom.:

Bravo

AF:

0.000654

Asia WGS

AF:

0.00465

AC:

AN:

3452

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 05, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jan 12, 2017

p.Thr523del in exon 13 of GPSM2: This variant is not expected to have clinical s ignificance because it has been identified in 1.8% (158/8654) of East Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs199964596). -

Chudley-McCullough syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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