7-7969477-G-C

Position:

• chr7-7969477-G-C

Variant summary

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

The NM_138426.4(GLCCI1):​c.127G>C​(p.Ala43Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: GLCCI1 NM_138426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.63

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=0.18682453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLCCI1	NM_138426.4	c.127G>C	p.Ala43Pro	missense_variant	1/8	ENST00000223145.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLCCI1	ENST00000223145.10	c.127G>C	p.Ala43Pro	missense_variant	1/8	1	NM_138426.4	P1
GLCCI1-DT	ENST00000428660.1	n.132+295C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 30

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 12, 2021

The c.127G>C (p.A43P) 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 127, causing the alanine (A) at amino acid position 43 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	Benign	0.092
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.32	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.42	N
REVEL	Benign	0.024
Sift	Benign	0.29	T
Sift4G	Benign	0.47	T
Polyphen		0.26	B
Vest4		0.38
MutPred		0.19		Gain of glycosylation at A43 (P = 0.0767);
MVP		0.28
MPC		0.94
ClinPred		0.52	D
GERP RS		0.84
Varity_R		0.10
gMVP		0.26

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: chr7-8009108;