chr1-108903423-C-G

Variant names:

• chr1-108903423-C-G
• rs338491
• NM_013296.5:c.1062+189C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013296.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPSM2	NM_013296.5	MANE Select	c.1062+189C>G		intron	N/A	NP_037428.3
	GPSM2	NM_001321038.2		c.1062+189C>G		intron	N/A	NP_001307967.1	P81274
	GPSM2	NM_001321039.3		c.1062+189C>G		intron	N/A	NP_001307968.1	P81274

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPSM2	ENST00000264126.9	TSL:1 MANE Select	c.1062+189C>G		intron	N/A	ENSP00000264126.3	P81274
	GPSM2	ENST00000674914.1		c.1113+189C>G		intron	N/A	ENSP00000501579.1	A0A6Q8PF02
	GPSM2	ENST00000675087.1		c.1113+189C>G		intron	N/A	ENSP00000502020.1	A0A6Q8PF02

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

African (AFR) AF: 0.584 AC: 24203 AN: 41420

American (AMR) AF: 0.248 AC: 3784 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3470

East Asian (EAS) AF: 0.0531 AC: 275 AN: 5182

South Asian (SAS) AF: 0.251 AC: 1213 AN: 4824

European-Finnish (FIN) AF: 0.305 AC: 3209 AN: 10506

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19587 AN: 67930

Other (OTH) AF: 0.317 AC: 668 AN: 2108

Alfa AF: 0.339 Hom.: 1188

Bravo AF: 0.362

Asia WGS AF: 0.209 AC: 729 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs338491; hg19: chr1-109446045;