chr1-108885722-G-GT

Variant names:

• chr1-108885722-G-GT
• rs150095508
• NM_013296.5:c.56+145dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013296.5(GPSM2):​c.56+145dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 648,348 control chromosomes in the GnomAD database, including 783 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (246 hom., cov: 32)
  • Exomes 𝑓: 0.040 (537 hom.)
• Consequence: GPSM2 NM_013296.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.587
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 1-108885722-G-GT is Benign according to our data. Variant chr1-108885722-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1265073.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0848 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+145dupT		intron	N/A	NP_037428.3
	GPSM2	NM_001321038.2		c.56+145dupT		intron	N/A	NP_001307967.1	P81274
	GPSM2	NM_001321039.3		c.56+145dupT		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+144_56+145insT		intron	N/A	ENSP00000264126.3	P81274
	GPSM2	ENST00000674914.1		c.13+144_13+145insT		intron	N/A	ENSP00000501579.1	A0A6Q8PF02
	GPSM2	ENST00000675087.1		c.13+144_13+145insT		intron	N/A	ENSP00000502020.1	A0A6Q8PF02

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8020 AN: 151986 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.0475

GnomAD4 exome AF: 0.0403 AC: 20019 AN: 496244 Hom.: 537 AF XY: 0.0408 AC XY: 10888 AN XY: 266978

African (AFR) AF: 0.0880 AC: 1213 AN: 13778

American (AMR) AF: 0.0235 AC: 569 AN: 24206

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 161 AN: 14874

East Asian (EAS) AF: 0.000593 AC: 20 AN: 33718

South Asian (SAS) AF: 0.0486 AC: 2303 AN: 47428

European-Finnish (FIN) AF: 0.0342 AC: 1381 AN: 40358

Middle Eastern (MID) AF: 0.0293 AC: 64 AN: 2188

European-Non Finnish (NFE) AF: 0.0451 AC: 13181 AN: 292572

Other (OTH) AF: 0.0416 AC: 1127 AN: 27122

GnomAD4 genome AF: 0.0529 AC: 8045 AN: 152104 Hom.: 246 Cov.: 32 AF XY: 0.0521 AC XY: 3872 AN XY: 74366

African (AFR) AF: 0.0871 AC: 3615 AN: 41488

American (AMR) AF: 0.0302 AC: 462 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 26 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.0459 AC: 221 AN: 4814

European-Finnish (FIN) AF: 0.0340 AC: 359 AN: 10564

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0468 AC: 3182 AN: 67988

Other (OTH) AF: 0.0494 AC: 104 AN: 2106

Alfa AF: 0.0498 Hom.: 25

Bravo AF: 0.0536

Asia WGS AF: 0.0400 AC: 140 AN: 3472

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
PhyloP100		-0.59
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: rs150095508; hg19: chr1-109428344;