chr1-209675827-G-T

Variant names:

• chr1-209675827-G-T
• NM_015714.4:c.143G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015714.4(G0S2):​c.143G>T​(p.Ser48Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: G0S2 NM_015714.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62
• Publications: 0 publications found

Genes affected

G0S2 (HGNC:30229): (G0/G1 switch 2) Involved in extrinsic apoptotic signaling pathway and positive regulation of extrinsic apoptotic signaling pathway. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

HSD11B1-AS1 (HGNC:54053): (HSD11B1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40782708).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015714.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G0S2	NM_015714.4	MANE Select	c.143G>T	p.Ser48Ile	missense	Exon 2 of 2	NP_056529.1	P27469
	HSD11B1-AS1	NR_134509.1		n.97-12766C>A		intron	N/A
	HSD11B1-AS1	NR_134510.1		n.67-12766C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G0S2	ENST00000367029.5	TSL:1 MANE Select	c.143G>T	p.Ser48Ile	missense	Exon 2 of 2	ENSP00000355996.4	P27469
	G0S2	ENST00000891678.1		c.143G>T	p.Ser48Ile	missense	Exon 2 of 2	ENSP00000561737.1
	G0S2	ENST00000891679.1		c.143G>T	p.Ser48Ile	missense	Exon 2 of 2	ENSP00000561738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	0.0044	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.19
Sift	Benign	0.084	T
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.38		Loss of disorder (P = 0.1401)
MVP		0.061
MPC		0.90
ClinPred		0.98	D
GERP RS		4.9
PromoterAI		-0.0080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.62
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-209849172;