rs778913696

Variant names:

• chr1-108898962-T-C
• rs778913696
• NM_013296.5:c.765T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-108898962-T-C
• chr1-108898962-T-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_013296.5(GPSM2):​c.765T>C​(p.Leu255Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L255L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPSM2 NM_013296.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.36 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPSM2	NM_013296.5	MANE Select	c.765T>C	p.Leu255Leu	synonymous	Exon 7 of 15	NP_037428.3
	GPSM2	NM_001321038.2		c.765T>C	p.Leu255Leu	synonymous	Exon 7 of 15	NP_001307967.1
	GPSM2	NM_001321039.3		c.765T>C	p.Leu255Leu	synonymous	Exon 7 of 16	NP_001307968.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPSM2	ENST00000264126.9	TSL:1 MANE Select	c.765T>C	p.Leu255Leu	synonymous	Exon 7 of 15	ENSP00000264126.3
	GPSM2	ENST00000674914.1		c.816T>C	p.Leu272Leu	synonymous	Exon 8 of 16	ENSP00000501579.1
	GPSM2	ENST00000675087.1		c.816T>C	p.Leu272Leu	synonymous	Exon 9 of 17	ENSP00000502020.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454622 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724114

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105596

Other (OTH) AF: 0.0000166 AC: 1 AN: 60106

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		0.36
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs778913696; hg19: chr1-109441584;