rs839859

Variant names:

• chr1-108927563-T-C
• rs839859
• NM_013296.5:c.1816-2138T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013296.5(GPSM2):​c.1816-2138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,058 control chromosomes in the GnomAD database, including 11,358 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11358 hom., cov: 32)
• Consequence: GPSM2 NM_013296.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM2	NM_013296.5	c.1816-2138T>C		intron_variant	Intron 14 of 14	ENST00000264126.9	NP_037428.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM2	ENST00000264126.9	c.1816-2138T>C		intron_variant	Intron 14 of 14	1	NM_013296.5	ENSP00000264126.3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54313 AN: 151940 Hom.: 11325 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.358 AC: 54404 AN: 152058 Hom.: 11358 Cov.: 32 AF XY: 0.353 AC XY: 26203 AN XY: 74322

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.317

Alfa AF: 0.301 Hom.: 5306

Bravo AF: 0.360

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.6
DANN	Benign	0.79

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: rs839859; hg19: chr1-109470185;