chrX-68716414-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142503.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD8	NM_001142503.3	MANE Select	c.280C>A	p.His94Asn	missense	Exon 5 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_001142504.3		c.40C>A	p.His14Asn	missense	Exon 4 of 14	NP_001135976.1	Q92502-1
	STARD8	NM_014725.5		c.40C>A	p.His14Asn	missense	Exon 4 of 14	NP_055540.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD8	ENST00000374599.8	TSL:1 MANE Select	c.280C>A	p.His94Asn	missense	Exon 5 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.40C>A	p.His14Asn	missense	Exon 4 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000374597.3	TSL:1	c.40C>A	p.His14Asn	missense	Exon 4 of 14	ENSP00000363725.3	Q92502-1

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

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 54086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40511

Middle Eastern (MID) AF: 0.00242 AC: 10 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841847

Other (OTH) AF: 0.0000217 AC: 1 AN: 46079

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.58
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.053
Sift	Benign	1.0	T
Sift4G	Benign	0.76	T
Polyphen		0.0020	B
Vest4		0.30
MutPred		0.34		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
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

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