16-11876132-T-C

Position:

• chr16-11876132-T-C

Variant summary

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

The ENST00000434724.7(GSPT1):​c.1646A>G​(p.Asn549Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSPT1 ENST00000434724.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.65

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15446797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSPT1	NM_002094.4	c.1646A>G	p.Asn549Ser	missense_variant	13/15	ENST00000434724.7	NP_002085.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSPT1	ENST00000434724.7	c.1646A>G	p.Asn549Ser	missense_variant	13/15	1	NM_002094.4	ENSP00000398131
RSL1D1-DT	ENST00000574364.2	n.467-19357T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

Sep 07, 2022

The c.1646A>G (p.N549S) alteration is located in exon 13 (coding exon 13) of the GSPT1 gene. This alteration results from a A to G substitution at nucleotide position 1646, causing the asparagine (N) at amino acid position 549 to be replaced by a serine (S). 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	0.062
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.027	.;.;T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.9	.;.;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.93	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.92	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0050	.;.;B;B
Vest4		0.64
MutPred		0.24		.;.;Gain of catalytic residue at G409 (P = 0.0995);Gain of catalytic residue at G409 (P = 0.0995);
MVP		0.43
MPC		1.1
ClinPred		0.79	D
GERP RS		5.0
Varity_R		0.24
gMVP		0.45

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: chr16-11969989;