Variant 5-65704375-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_019072.3(SGTB):c.278A>G(p.Asn93Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000807 in 1,610,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SGTB
NM_019072.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

Variant links:

Genes affected

SGTB (HGNC:23567): (small glutamine rich tetratricopeptide repeat co-chaperone beta) Predicted to enable molecular adaptor activity. Predicted to be involved in positive regulation of chaperone-mediated protein folding; posttranslational protein targeting to endoplasmic reticulum membrane; and ubiquitin-dependent ERAD pathway. Predicted to be part of TRC complex. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SGTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGTB	NM_019072.3 linkuse as main transcript	c.278A>G	p.Asn93Ser	missense_variant	5/11	ENST00000381007.9	NP_061945.1	Q96EQ0
SGTB	XM_005248548.4 linkuse as main transcript	c.278A>G	p.Asn93Ser	missense_variant	5/11		XP_005248605.1	Q96EQ0
SGTB	XM_047417334.1 linkuse as main transcript	c.83A>G	p.Asn28Ser	missense_variant	4/10		XP_047273290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGTB	ENST00000381007.9 linkuse as main transcript	c.278A>G	p.Asn93Ser	missense_variant	5/11	1	NM_019072.3	ENSP00000370395.4		Q96EQ0
SGTB	ENST00000506816.1 linkuse as main transcript	c.278A>G	p.Asn93Ser	missense_variant	5/7	3		ENSP00000421447.1		D6RFW1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1458078

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725478

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

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

AF:

0.0000328

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2023

The c.278A>G (p.N93S) alteration is located in exon 5 (coding exon 4) of the SGTB gene. This alteration results from a A to G substitution at nucleotide position 278, causing the asparagine (N) at amino acid position 93 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

Pathogenic

0.96

BayesDel_addAF

Benign

0.0016

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

T;T

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Uncertain

0.13

MutationAssessor

Pathogenic

3.0

M;.

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Pathogenic

0.66

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;.

Polyphen

1.0

D;.

Vest4

0.84

MVP

0.90

MPC

1.5

ClinPred

1.0

GERP RS

5.5

Varity_R

0.80

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over