1-53514695-G-A

Position:

• chr1-53514695-G-A

Variant summary

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

The NM_001367484.1(GLIS1):​c.1813C>T​(p.Pro605Ser) 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. 13/21 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: GLIS1 NM_001367484.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

Genes affected

GLIS1 (HGNC:29525): (GLIS family zinc finger 1) GLIS1 is a GLI (MIM 165220)-related Kruppel-like zinc finger protein that functions as an activator and repressor of transcription (Kim et al., 2002 [PubMed 12042312]).[supplied by OMIM, Mar 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=0.16831258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS1	NM_001367484.1	c.1813C>T	p.Pro605Ser	missense_variant	8/11	ENST00000628545.2	NP_001354413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIS1	ENST00000628545.2	c.1813C>T	p.Pro605Ser	missense_variant	8/11	5	NM_001367484.1	ENSP00000486112.1
GLIS1	ENST00000312233.4	c.1288C>T	p.Pro430Ser	missense_variant	7/10	2		ENSP00000309653.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 09, 2024

The c.1288C>T (p.P430S) alteration is located in exon 7 (coding exon 5) of the GLIS1 gene. This alteration results from a C to T substitution at nucleotide position 1288, causing the proline (P) at amino acid position 430 to be replaced by a serine (S). 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	Benign	0.088
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.086	T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.61	N;.
REVEL	Benign	0.019
Sift	Benign	0.084	T;.
Sift4G	Benign	0.74	T;T
Polyphen		0.0090	B;.
Vest4		0.32
MutPred		0.18		Gain of glycosylation at P430 (P = 0.0161);.;
MVP		0.41
MPC		0.051
ClinPred		0.13	T
GERP RS		2.0
Varity_R		0.029
gMVP		0.32

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: chr1-53980368;