Variant chr2-96192399-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020151.4(STARD7):c.813G>A(p.Met271Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,636 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

STARD7
NM_020151.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.09

Variant links:

Genes affected

STARD7 (HGNC:18063): (StAR related lipid transfer domain containing 7) Predicted to enable lipid binding activity. Predicted to act upstream of or within several processes, including establishment of skin barrier; mucociliary clearance; and myeloid dendritic cell activation. Predicted to be located in cytoplasm and extracellular region. Implicated in familial adult myoclonic epilepsy 2. [provided by Alliance of Genome Resources, Apr 2022]

STARD7 links:

STARD7 (HGNC:):

STARD7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD7	NM_020151.4 linkuse as main transcript	c.813G>A	p.Met271Ile	missense_variant	6/8	ENST00000337288.10	NP_064536.2	Q9NQZ5
STARD7	NM_001385622.1 linkuse as main transcript	c.510G>A	p.Met170Ile	missense_variant	6/8		NP_001372551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STARD7	ENST00000337288.10 linkuse as main transcript	c.813G>A	p.Met271Ile	missense_variant	6/8	1	NM_020151.4	ENSP00000338030.5		Q9NQZ5
STARD7	ENST00000462501.1 linkuse as main transcript	n.473G>A		non_coding_transcript_exon_variant	5/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000478

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461560

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727086

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:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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:

0.000478

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.0000416

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 12, 2021

The c.813G>A (p.M271I) alteration is located in exon 6 (coding exon 6) of the STARD7 gene. This alteration results from a G to A substitution at nucleotide position 813, causing the methionine (M) at amino acid position 271 to be replaced by an isoleucine (I). 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

0.99

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.017

Polyphen

0.96

Vest4

0.79

MutPred

0.84

Loss of disorder (P = 0.065);

MVP

0.48

MPC

1.6

ClinPred

0.99

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.64

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