16-11875857-G-C

Position:

• chr16-11875857-G-C

Variant summary

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

The ENST00000434724.7(GSPT1):​c.1765C>G​(p.Gln589Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSPT1 ENST00000434724.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.57

Genes affected

GSPT1 (HGNC:4621): (G1 to S phase transition 1) Enables translation release factor activity. Involved in regulation of translational termination. Acts upstream of or within protein methylation. Predicted to be located in cytosol. Predicted to be part of translation release factor complex. [provided by Alliance of Genome Resources, Apr 2022]

RSL1D1-DT (HGNC:55337): (RSL1D1 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSPT1	NM_002094.4	c.1765C>G	p.Gln589Glu	missense_variant	14/15	ENST00000434724.7	NP_002085.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSPT1	ENST00000434724.7	c.1765C>G	p.Gln589Glu	missense_variant	14/15	1	NM_002094.4	ENSP00000398131
RSL1D1-DT	ENST00000574364.2	n.467-19632G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

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

Aug 20, 2023

The c.1765C>G (p.Q589E) alteration is located in exon 14 (coding exon 14) of the GSPT1 gene. This alteration results from a C to G substitution at nucleotide position 1765, causing the glutamine (Q) at amino acid position 589 to be replaced by a glutamic acid (E). 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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.057	.;.;T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D;D;.;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.88	.;.;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.71	T;T;T;T
Polyphen		0.087	.;.;B;B
Vest4		0.64
MutPred		0.53		.;.;Loss of MoRF binding (P = 0.0355);Loss of MoRF binding (P = 0.0355);
MVP		0.68
MPC		1.5
ClinPred		0.78	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.41
gMVP		0.84

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: chr16-11969714;