7-7969793-C-T

Position:

• chr7-7969793-C-T

Variant summary

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

The NM_138426.4(GLCCI1):​c.443C>T​(p.Ser148Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000451 in 1,330,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: GLCCI1 NM_138426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.44

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21031496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLCCI1	NM_138426.4	c.443C>T	p.Ser148Leu	missense_variant	1/8	ENST00000223145.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLCCI1	ENST00000223145.10	c.443C>T	p.Ser148Leu	missense_variant	1/8	1	NM_138426.4	P1
GLCCI1-DT	ENST00000428660.1	n.111G>A		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000451 AC: 6 AN: 1330604 Hom.: 0 Cov.: 33 AF XY: 0.00000609 AC XY: 4 AN XY: 656850

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: 0.00000570

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 28, 2023

The c.443C>T (p.S148L) alteration is located in exon 1 (coding exon 1) of the GLCCI1 gene. This alteration results from a C to T substitution at nucleotide position 443, causing the serine (S) at amino acid position 148 to be replaced by a leucine (L). 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	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.3	N;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.045	B;.;.
Vest4		0.46
MutPred		0.24		Loss of phosphorylation at S148 (P = 0.0065);.;.;
MVP		0.41
MPC		0.53
ClinPred		0.88	D
GERP RS		2.4
Varity_R		0.19
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr7-8009424;