1-108885627-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013296.5(GPSM2):c.56+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,124,092 control chromosomes in the GnomAD database, including 49,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (10032 hom., cov: 32)
  • Exomes 𝑓: 0.27 (39146 hom.)
• Consequence: GPSM2 NM_013296.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.851

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-108885627-G-A is Benign according to our data. Variant chr1-108885627-G-A is described in ClinVar as [Benign]. Clinvar id is 1269298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPSM2	NM_013296.5	c.56+49G>A		intron_variant		ENST00000264126.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPSM2	ENST00000264126.9	c.56+49G>A		intron_variant		1	NM_013296.5	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51811 AN: 151844 Hom.: 10000 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.308

GnomAD3 exomes AF: 0.275 AC: 67768 AN: 246266 Hom.: 10455 AF XY: 0.273 AC XY: 36455 AN XY: 133330

Gnomad AFR exome AF: 0.526

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.329

Gnomad EAS exome AF: 0.0585

Gnomad SAS exome AF: 0.263

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.279

GnomAD4 exome AF: 0.273 AC: 265508 AN: 972130 Hom.: 39146 Cov.: 13 AF XY: 0.274 AC XY: 138081 AN XY: 504496

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.0600

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.342 AC: 51896 AN: 151962 Hom.: 10032 Cov.: 32 AF XY: 0.337 AC XY: 25008 AN XY: 74274

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.308

Alfa AF: 0.303 Hom.: 2725

Bravo AF: 0.343

Asia WGS AF: 0.202 AC: 701 AN: 3470

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

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	12
Dann	Benign	0.53

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: rs10857987; hg19: chr1-109428249;