12-75481891-T-C

Position:

• chr12-75481891-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006851.3(GLIPR1):​c.232T>C​(p.Ser78Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLIPR1 NM_006851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.39

Genes affected

GLIPR1 (HGNC:17001): (GLI pathogenesis related 1) This gene encodes a protein with similarity to both the pathogenesis-related protein (PR) superfamily and the cysteine-rich secretory protein (CRISP) family. Increased expression of this gene is associated with myelomocytic differentiation in macrophage and decreased expression of this gene through gene methylation is associated with prostate cancer. The protein has proapoptotic activities in prostate and bladder cancer cells. This gene is a member of a cluster on chromosome 12 containing two other similar genes. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07137987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIPR1	NM_006851.3	c.232T>C	p.Ser78Pro	missense_variant	2/6	ENST00000266659.8	NP_006842.2
GLIPR1	XM_047428131.1	c.232T>C	p.Ser78Pro	missense_variant	2/3		XP_047284087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIPR1	ENST00000266659.8	c.232T>C	p.Ser78Pro	missense_variant	2/6	1	NM_006851.3	ENSP00000266659.3
GLIPR1	ENST00000456650.7	c.232T>C	p.Ser78Pro	missense_variant	2/6	1		ENSP00000391144.3
GLIPR1	ENST00000550491	c.-121T>C		5_prime_UTR_variant	2/4	3		ENSP00000448008.1
GLIPR1	ENST00000536703.5	n.232T>C		non_coding_transcript_exon_variant	2/4	2		ENSP00000440595.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.232T>C (p.S78P) alteration is located in exon 2 (coding exon 2) of the GLIPR1 gene. This alteration results from a T to C substitution at nucleotide position 232, causing the serine (S) at amino acid position 78 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.9
DANN	Benign	0.62
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.13
Sift	Benign	0.20	T;D
Sift4G	Benign	0.16	T;D
Polyphen		0.66	P;B
Vest4		0.36
MutPred		0.55		Loss of MoRF binding (P = 0.0858);Loss of MoRF binding (P = 0.0858);
MVP		0.15
MPC		0.27
ClinPred		0.16	T
GERP RS		-12
Varity_R		0.53
gMVP		0.44

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-75875671;