1-108885533-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_013296.5(GPSM2):c.11A>T(p.Asn4Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPSM2 NM_013296.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.27

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]

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15093485).
• BP6: Variant 1-108885533-A-T is Benign according to our data. Variant chr1-108885533-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3065632.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPSM2	NM_013296.5	c.11A>T	p.Asn4Ile	missense_variant	2/15	ENST00000264126.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPSM2	ENST00000264126.9	c.11A>T	p.Asn4Ile	missense_variant	2/15	1	NM_013296.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1421874 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 709972

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Chudley-McCullough syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.17	T;.;.;T;T;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.0	N;.;.;N;N;.;.;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.3	N;.;N;.;N;.;N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0040	D;.;D;.;D;.;D;D
Sift4G	Uncertain	0.013	D;.;D;.;D;.;D;D
Polyphen		0.0030	B;.;.;B;B;.;.;.
Vest4		0.31
MutPred		0.23		Loss of disorder (P = 0.1171);Loss of disorder (P = 0.1171);Loss of disorder (P = 0.1171);Loss of disorder (P = 0.1171);Loss of disorder (P = 0.1171);Loss of disorder (P = 0.1171);Loss of disorder (P = 0.1171);Loss of disorder (P = 0.1171);
MVP		0.93
MPC		0.30
ClinPred		0.37	T
GERP RS		3.0
Varity_R		0.14
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-109428155;