16-85634043-C-G

Position:

• chr16-85634043-C-G

Variant summary

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

The NM_014615.5(GSE1):​c.137C>G​(p.Thr46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GSE1 NM_014615.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

Genes affected

GSE1 (HGNC:28979): (Gse1 coiled-coil protein) This gene encodes a proline-rich protein with coiled coil domains that may be a subunit of a BRAF35-HDAC (BHC) histone deacetylase complex. This gene may function as an oncogene in breast cancer and enhanced expression of the encoded protein has been observed in breast cancer patients. [provided by RefSeq, May 2017]

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=0.07502413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSE1	NM_014615.5	c.137C>G	p.Thr46Ser	missense_variant	2/16	ENST00000253458.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSE1	ENST00000253458.12	c.137C>G	p.Thr46Ser	missense_variant	2/16	5	NM_014615.5	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Oct 05, 2021

The c.137C>G (p.T46S) alteration is located in exon 2 (coding exon 2) of the GSE1 gene. This alteration results from a C to G substitution at nucleotide position 137, causing the threonine (T) at amino acid position 46 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	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.51	T
Polyphen		0.0010	.;B
Vest4		0.30
MutPred		0.098		.;Gain of phosphorylation at T46 (P = 0.0455);
MVP		0.22
ClinPred		0.22	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.10
gMVP		0.12

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: chr16-85667649;