NM_013296.5:c.56+49G>A

Variant names:

• chr1-108885627-G-A
• rs10857987
• NM_013296.5:c.56+49G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.851
• Publications: 4 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 -20 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 VariationId is 1269298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 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.56+49G>A		intron	N/A	NP_037428.3
	GPSM2	NM_001321038.2		c.56+49G>A		intron	N/A	NP_001307967.1	P81274
	GPSM2	NM_001321039.3		c.56+49G>A		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.56+49G>A		intron	N/A	ENSP00000264126.3	P81274
	GPSM2	ENST00000674914.1		c.13+49G>A		intron	N/A	ENSP00000501579.1	A0A6Q8PF02
	GPSM2	ENST00000675087.1		c.13+49G>A		intron	N/A	ENSP00000502020.1	A0A6Q8PF02

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

GnomAD2 exomes AF: 0.275 AC: 67768 AN: 246266 AF XY: 0.273

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 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

African (AFR) AF: 0.525 AC: 12610 AN: 24010

American (AMR) AF: 0.223 AC: 9708 AN: 43580

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 7581 AN: 22964

East Asian (EAS) AF: 0.0600 AC: 2245 AN: 37422

South Asian (SAS) AF: 0.263 AC: 19883 AN: 75604

European-Finnish (FIN) AF: 0.300 AC: 15866 AN: 52962

Middle Eastern (MID) AF: 0.298 AC: 1434 AN: 4808

European-Non Finnish (NFE) AF: 0.276 AC: 183903 AN: 666620

Other (OTH) AF: 0.278 AC: 12278 AN: 44160

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

African (AFR) AF: 0.525 AC: 21762 AN: 41422

American (AMR) AF: 0.242 AC: 3693 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1156 AN: 3464

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

South Asian (SAS) AF: 0.251 AC: 1209 AN: 4816

European-Finnish (FIN) AF: 0.306 AC: 3219 AN: 10534

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19523 AN: 67960

Other (OTH) AF: 0.308 AC: 649 AN: 2108

Alfa AF: 0.304 Hom.: 3357

Bravo AF: 0.343

Asia WGS AF: 0.202 AC: 701 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.53
PhyloP100		0.85
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: rs10857987; hg19: chr1-109428249;