Variant 2-96186798-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020151.4(STARD7):c.1045G>T(p.Ala349Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

STARD7
NM_020151.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.53

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:

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ACMG classification

Classification made for transcript

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=0.037707746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD7	NM_020151.4 linkuse as main transcript	c.1045G>T	p.Ala349Ser	missense_variant	8/8	ENST00000337288.10	NP_064536.2	Q9NQZ5
STARD7	NM_001385622.1 linkuse as main transcript	c.742G>T	p.Ala248Ser	missense_variant	8/8		NP_001372551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STARD7	ENST00000337288.10 linkuse as main transcript	c.1045G>T	p.Ala349Ser	missense_variant	8/8	1	NM_020151.4	ENSP00000338030.5	Q9NQZ5
STARD7	ENST00000462501.1 linkuse as main transcript	n.705G>T		non_coding_transcript_exon_variant	7/7	2
STARD7	ENST00000479456.1 linkuse as main transcript	n.1018G>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

The STARD7 p.A349S variant was not identified in the literature nor was it identified in dbSNP or ClinVar. The variant was identified in control databases in 1 of 31396 chromosomes at a frequency of 0.00003185 (Genome Aggregation Database March 6, 2019, v2.1.1). The p.A349 residue is conserved in mammals however computational analyses (MUT Assesor, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0066

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

M_CAP

Benign

0.0044

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.11

REVEL

Benign

0.032

Sift

Benign

0.40

Sift4G

Benign

0.41

Polyphen

0.043

Vest4

0.045

MutPred

0.28

Gain of phosphorylation at A349 (P = 0.0023);

MVP

0.15

MPC

0.56

ClinPred

0.13

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.67

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