Variant 18-54329398-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_139171.2(STARD6):c.428A>G(p.Tyr143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 1,452,936 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

STARD6
NM_139171.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Variant links:

Genes affected

STARD6 (HGNC:18066): (StAR related lipid transfer domain containing 6) Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1; MIM 184756) and by liver X receptors (e.g., LXRA; MIM 602423). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR; MIM 600617). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD6 (Soccio et al., 2002 [PubMed 12011452]).[supplied by OMIM, Mar 2008]

STARD6 links:

Genome browser will be placed here

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=0.3965538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STARD6	NM_139171.2 linkuse as main transcript	c.428A>G	p.Tyr143Cys	missense_variant	7/8	ENST00000307844.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
STARD6	ENST00000307844.4 linkuse as main transcript	c.428A>G	p.Tyr143Cys	missense_variant	7/8	1	NM_139171.2	P2
STARD6	ENST00000686109.1 linkuse as main transcript	c.461A>G	p.Tyr154Cys	missense_variant	8/9			A2
STARD6	ENST00000581310.5 linkuse as main transcript	c.428A>G	p.Tyr143Cys	missense_variant	8/9	5		P2
STARD6	ENST00000689888.1 linkuse as main transcript	c.*484A>G		3_prime_UTR_variant, NMD_transcript_variant	7/8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242514

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000757

AC:

AN:

1452936

Hom.:

Cov.:

AF XY:

0.00000969

AC XY:

AN XY:

722558

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:

0.000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 27, 2021

The c.428A>G (p.Y143C) alteration is located in exon 5 (coding exon 5) of the STARD6 gene. This alteration results from a A to G substitution at nucleotide position 428, causing the tyrosine (Y) at amino acid position 143 to be replaced by a cysteine (C). 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

0.084

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

T;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.57

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.40

T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.83

D;D;D

PrimateAI

Uncertain

0.62

Sift4G

Benign

0.081

T;T

Polyphen

0.44

B;B

Vest4

0.26

MutPred

0.69

Loss of disorder (P = 0.0965);Loss of disorder (P = 0.0965);

MVP

0.91

MPC

0.23

ClinPred

0.80

GERP RS

4.4

Varity_R

0.21

gMVP

0.56

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

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