16-11896620-A-G

Position:

• chr16-11896620-A-G

Variant summary

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

The ENST00000434724.7(GSPT1):​c.602T>C​(p.Val201Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,774 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GSPT1 ENST00000434724.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12

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.602T>C	p.Val201Ala	missense_variant	4/15	ENST00000434724.7	NP_002085.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSPT1	ENST00000434724.7	c.602T>C	p.Val201Ala	missense_variant	4/15	1	NM_002094.4	ENSP00000398131
RSL1D1-DT	ENST00000574364.2	n.589+1009A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457774 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724654

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jan 04, 2022

The c.602T>C (p.V201A) alteration is located in exon 4 (coding exon 4) of the GSPT1 gene. This alteration results from a T to C substitution at nucleotide position 602, causing the valine (V) at amino acid position 201 to be replaced by an alanine (A). 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	0.069
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.017	.;.;T;T;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.71	T;T;.;T;T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.069	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	.;.;L;L;.;.
MutationTaster	Benign	0.93	D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.10	N;N;N;N;N;N
REVEL	Benign	0.075
Sift	Benign	0.56	T;T;T;T;T;T
Sift4G	Benign	0.64	T;T;T;T;.;D
Polyphen		0.0	.;.;B;B;.;.
Vest4		0.18
MutPred		0.10		.;.;Gain of loop (P = 0);Gain of loop (P = 0);.;.;
MVP		0.26
MPC		0.39
ClinPred		0.29	T
GERP RS		4.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.8
Varity_R		0.023
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: -14

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: chr16-11990477;