7-7969664-G-C

Position:

• chr7-7969664-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_138426.4(GLCCI1):​c.314G>C​(p.Ser105Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000011 in 912,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S105R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: GLCCI1 NM_138426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

Genes affected

GLCCI1 (HGNC:18713): (glucocorticoid induced 1) This gene encodes a protein of unknown function. Expression of this gene is induced by glucocorticoids and may be an early marker for glucocorticoid-induced apoptosis. Single nucleotide polymorphisms in this gene are associated with a decreased response to inhaled glucocorticoids in asthmatic patients. [provided by RefSeq, Feb 2012]

GLCCI1-DT (HGNC:40852): (GLCCI1 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity GLCI1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07794827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLCCI1	NM_138426.4	c.314G>C	p.Ser105Thr	missense_variant	1/8	ENST00000223145.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLCCI1	ENST00000223145.10	c.314G>C	p.Ser105Thr	missense_variant	1/8	1	NM_138426.4	P1
GLCCI1-DT	ENST00000428660.1	n.132+108C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000110 AC: 1 AN: 912694 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 437018

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000188

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.: 31

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

Dec 17, 2023

The c.314G>C (p.S105T) alteration is located in exon 1 (coding exon 1) of the GLCCI1 gene. This alteration results from a G to C substitution at nucleotide position 314, causing the serine (S) at amino acid position 105 to be replaced by a threonine (T). 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	0.085
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	0.93	D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.020
Sift	Benign	0.31	T
Sift4G	Uncertain	0.043	D
Polyphen		0.015	B
Vest4		0.10
MutPred		0.23		Loss of relative solvent accessibility (P = 0.0981);
MVP		0.20
MPC		0.40
ClinPred		0.086	T
GERP RS		0.38
Varity_R		0.052
gMVP		0.47

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: chr7-8009295;