1-108885722-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013296.5(GPSM2):c.56+145dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 648,348 control chromosomes in the GnomAD database, including 783 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (246 hom., cov: 32)
  • Exomes 𝑓: 0.040 (537 hom.)
• Consequence: GPSM2 NM_013296.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.587

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]

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-108885722-G-GT is Benign according to our data. Variant chr1-108885722-G-GT is described in ClinVar as [Benign]. Clinvar id is 1265073.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPSM2	NM_013296.5	c.56+145dup		intron_variant		ENST00000264126.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPSM2	ENST00000264126.9	c.56+145dup		intron_variant		1	NM_013296.5	P1

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8020 AN: 151986 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.0475

GnomAD4 exome AF: 0.0403 AC: 20019 AN: 496244 Hom.: 537 AF XY: 0.0408 AC XY: 10888 AN XY: 266978

Gnomad4 AFR exome AF: 0.0880

Gnomad4 AMR exome AF: 0.0235

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.000593

Gnomad4 SAS exome AF: 0.0486

Gnomad4 FIN exome AF: 0.0342

Gnomad4 NFE exome AF: 0.0451

Gnomad4 OTH exome AF: 0.0416

GnomAD4 genome AF: 0.0529 AC: 8045 AN: 152104 Hom.: 246 Cov.: 32 AF XY: 0.0521 AC XY: 3872 AN XY: 74366

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0468

Gnomad4 OTH AF: 0.0494

Alfa AF: 0.0498 Hom.: 25

Bravo AF: 0.0536

Asia WGS AF: 0.0400 AC: 140 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs150095508; hg19: chr1-109428344;