X-68716414-C-A

Variant names:

• chrX-68716414-C-A
• rs972737201
• NM_001142503.3:c.280C>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001142503.3(STARD8):​c.280C>A​(p.His94Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,097,822 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.582

Genes affected

STARD8 (HGNC:19161): (StAR related lipid transfer domain containing 8) This gene encodes a member of a subfamily of Rho GTPase activating proteins that contain a steroidogenic acute regulatory protein related lipid transfer domain. The encoded protein localizes to focal adhesions and may be involved in regulating cell morphology. This protein may also function as a tumor suppressor. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06586197).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD8	NM_001142503.3	c.280C>A	p.His94Asn	missense_variant	Exon 5 of 15	ENST00000374599.8	NP_001135975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD8	ENST00000374599.8	c.280C>A	p.His94Asn	missense_variant	Exon 5 of 15	1	NM_001142503.3	ENSP00000363727.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1097822 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 3 AN XY: 363182

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: 0.0000217

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.280C>A (p.H94N) alteration is located in exon 5 (coding exon 5) of the STARD8 gene. This alteration results from a C to A substitution at nucleotide position 280, causing the histidine (H) at amino acid position 94 to be replaced by an asparagine (N). 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	0.090
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.0071	T;.;T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.77	T;T;.
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.030	N;N;N
REVEL	Benign	0.053
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.76	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.30
MutPred		0.34		Loss of sheet (P = 3e-04);.;Loss of sheet (P = 3e-04);
MVP		0.50
MPC		0.067
ClinPred		0.14	T
GERP RS		3.8
Varity_R		0.22
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs972737201; hg19: chrX-67936256; COSMIC: COSV99366833;