chr1-209675961-G-T

Variant names:

• chr1-209675961-G-T
• rs145782263
• NM_015714.4:c.277G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015714.4(G0S2):​c.277G>T​(p.Gly93Cys) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G93S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: G0S2 NM_015714.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041469246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G0S2	NM_015714.4	c.277G>T	p.Gly93Cys	missense_variant	Exon 2 of 2	ENST00000367029.5	NP_056529.1
HSD11B1-AS1	NR_134509.1	n.97-12900C>A		intron_variant	Intron 1 of 2
HSD11B1-AS1	NR_134510.1	n.67-12900C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G0S2	ENST00000367029.5	c.277G>T	p.Gly93Cys	missense_variant	Exon 2 of 2	1	NM_015714.4	ENSP00000355996.4
HSD11B1-AS1	ENST00000441672.1	n.97-12900C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1405270 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 691528

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.1
DANN	Benign	0.80
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.017
Sift	Benign	0.16	T
Sift4G	Benign	0.17	T
Polyphen		0.010	B
Vest4		0.058
MutPred		0.24		Loss of MoRF binding (P = 0.0763);
MVP		0.048
MPC		0.33
ClinPred		0.072	T
GERP RS		-5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs145782263; hg19: chr1-209849306;