rs12028832

Variant names:

• chr1-108898118-A-G
• rs12028832
• NM_013296.5:c.557+17A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013296.5(GPSM2):​c.557+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,611,010 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (80 hom., cov: 32)
  • Exomes 𝑓: 0.014 (323 hom.)
• Consequence: GPSM2 NM_013296.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.460

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]

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-108898118-A-G is Benign according to our data. Variant chr1-108898118-A-G is described in ClinVar as [Benign]. Clinvar id is 260281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM2	NM_013296.5	c.557+17A>G		intron_variant	Intron 5 of 14	ENST00000264126.9	NP_037428.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM2	ENST00000264126.9	c.557+17A>G		intron_variant	Intron 5 of 14	1	NM_013296.5	ENSP00000264126.3

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3750 AN: 152186 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00998

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0188 AC: 4718 AN: 251082 Hom.: 102 AF XY: 0.0199 AC XY: 2704 AN XY: 135708

Gnomad AFR exome AF: 0.0554

Gnomad AMR exome AF: 0.00980

Gnomad ASJ exome AF: 0.0276

Gnomad EAS exome AF: 0.0171

Gnomad SAS exome AF: 0.0521

Gnomad FIN exome AF: 0.00152

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.0184

GnomAD4 exome AF: 0.0135 AC: 19695 AN: 1458706 Hom.: 323 Cov.: 30 AF XY: 0.0147 AC XY: 10654 AN XY: 725948

Gnomad4 AFR exome AF: 0.0571

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0273

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.0518

Gnomad4 FIN exome AF: 0.00197

Gnomad4 NFE exome AF: 0.00910

Gnomad4 OTH exome AF: 0.0184

GnomAD4 genome AF: 0.0248 AC: 3776 AN: 152304 Hom.: 80 Cov.: 32 AF XY: 0.0254 AC XY: 1892 AN XY: 74476

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.0582

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0148 Hom.: 29

Bravo AF: 0.0262

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 14, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs12028832; hg19: chr1-109440740;