rs839859

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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.

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.1816-2138T>C		intron	N/A	NP_037428.3
	GPSM2	NM_001321038.2		c.1816-2138T>C		intron	N/A	NP_001307967.1	P81274
	GPSM2	NM_001321039.3		c.1816-2138T>C		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.1816-2138T>C		intron	N/A	ENSP00000264126.3	P81274
	CLCC1	ENST00000685014.1		c.*4984A>G		3_prime_UTR	Exon 12 of 12	ENSP00000510582.1	Q96S66-1
	CLCC1	ENST00000685104.1		c.*4984A>G		3_prime_UTR	Exon 13 of 13	ENSP00000508473.1	Q96S66-1

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

African (AFR) AF: 0.573 AC: 23736 AN: 41460

American (AMR) AF: 0.251 AC: 3833 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3472

East Asian (EAS) AF: 0.0542 AC: 281 AN: 5186

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4818

European-Finnish (FIN) AF: 0.309 AC: 3261 AN: 10550

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19783 AN: 67992

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.312 Hom.: 7609

Bravo AF: 0.360

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.6
DANN	Benign	0.79
PhyloP100		0.21
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: rs839859; hg19: chr1-109470185;