Variant 19-2757705-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003021.4(SGTA):c.815G>C(p.Ser272Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S272G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SGTA
NM_003021.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

Variant links:

Genes affected

SGTA (HGNC:10819): (small glutamine rich tetratricopeptide repeat co-chaperone alpha) This gene encodes a protein which is capable of interacting with the major nonstructural protein of parvovirus H-1 and 70-kDa heat shock cognate protein; however, its function is not known. Since this transcript is expressed ubiquitously in various tissues, this protein may serve a housekeeping function. [provided by RefSeq, Jul 2008]

SGTA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.277841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGTA	NM_003021.4 linkuse as main transcript	c.815G>C	p.Ser272Thr	missense_variant	10/12	ENST00000221566.7
SGTA	XM_011528178.4 linkuse as main transcript	c.815G>C	p.Ser272Thr	missense_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGTA	ENST00000221566.7 linkuse as main transcript	c.815G>C	p.Ser272Thr	missense_variant	10/12	1	NM_003021.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1436040

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712450

show subpopulations

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:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Apr 24, 2023

The c.815G>C (p.S272T) alteration is located in exon 10 (coding exon 9) of the SGTA gene. This alteration results from a G to C substitution at nucleotide position 815, causing the serine (S) at amino acid position 272 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.32

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.021

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

M_CAP

Benign

0.0088

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.3

REVEL

Benign

0.052

Sift

Benign

0.19

Sift4G

Benign

0.35

Polyphen

0.049

Vest4

0.37

MutPred

0.32

Gain of helix (P = 0.2059);

MVP

0.54

MPC

0.48

ClinPred

0.60

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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