chr16-74463442-T-C

Position:

• chr16-74463442-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145667.2(GLG1):​c.2705A>G​(p.Gln902Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,368 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GLG1 NM_001145667.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25

Genes affected

GLG1 (HGNC:4316): (golgi glycoprotein 1) Predicted to enable fibroblast growth factor binding activity. Predicted to act upstream of or within several processes, including negative regulation of protein processing; negative regulation of transforming growth factor beta receptor signaling pathway; and regulation of chondrocyte differentiation. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36861888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLG1	NM_001145667.2	c.2705A>G	p.Gln902Arg	missense_variant	20/26	ENST00000422840.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLG1	ENST00000422840.7	c.2705A>G	p.Gln902Arg	missense_variant	20/26	1	NM_001145667.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461368 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727052

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

Jun 21, 2023

The c.2705A>G (p.Q902R) alteration is located in exon 20 (coding exon 20) of the GLG1 gene. This alteration results from a A to G substitution at nucleotide position 2705, causing the glutamine (Q) at amino acid position 902 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.35	T;T;T
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.86	P;B;.
Vest4		0.50
MutPred		0.68		Gain of MoRF binding (P = 0.0109);Gain of MoRF binding (P = 0.0109);.;
MVP		0.28
MPC		0.52
ClinPred		0.74	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.51

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: chr16-74497340;