rs338491

chr1-108903423-C-G

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.1062+189C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,902 control chromosomes in the GnomAD database, including 11,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (11490 hom., cov: 31)
• Consequence: GPSM2 NM_013296.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.345

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 1-108903423-C-G is Benign according to our data. Variant chr1-108903423-C-G is described in ClinVar as [Benign]. Clinvar id is 681360.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPSM2	NM_013296.5	c.1062+189C>G		intron_variant		ENST00000264126.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPSM2	ENST00000264126.9	c.1062+189C>G		intron_variant		1	NM_013296.5	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54457 AN: 151784 Hom.: 11457 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.359 AC: 54543 AN: 151902 Hom.: 11490 Cov.: 31 AF XY: 0.354 AC XY: 26293 AN XY: 74236

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.317

Alfa AF: 0.339 Hom.: 1188

Bravo AF: 0.362

Asia WGS AF: 0.209 AC: 729 AN: 3478

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 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.3
Dann	Benign	0.63

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: rs338491; hg19: chr1-109446045;