X-68717533-C-T

Variant names:

• chrX-68717533-C-T
• rs779092501
• NM_001142503.3:c.619C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001142503.3(STARD8):​c.619C>T​(p.Arg207Cys) 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 1,097,578 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R207H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000010 (0 hom. 4 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.091695756).
• BS2: High Hemizygotes in GnomAdExome4 at 4 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.619C>T	p.Arg207Cys	missense	Exon 6 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_001142504.3		c.379C>T	p.Arg127Cys	missense	Exon 5 of 14	NP_001135976.1	Q92502-1
	STARD8	NM_014725.5		c.379C>T	p.Arg127Cys	missense	Exon 5 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.619C>T	p.Arg207Cys	missense	Exon 6 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.379C>T	p.Arg127Cys	missense	Exon 5 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000374597.3	TSL:1	c.379C>T	p.Arg127Cys	missense	Exon 5 of 14	ENSP00000363725.3	Q92502-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000384 AC: 7 AN: 182411 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000730

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000361

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1097578 Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 4 AN XY: 363072

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.0000568 AC: 2 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.000132 AC: 4 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39851

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000475 AC: 4 AN: 842145

Other (OTH) AF: 0.0000217 AC: 1 AN: 46097

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

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	0.079
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.4
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.063
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.028	D
Polyphen		0.0040	B
Vest4		0.13
MutPred		0.28		Loss of methylation at K122 (P = 0.0711)
MVP		0.72
MPC		0.083
ClinPred		0.26	T
GERP RS		0.43
Varity_R		0.38
gMVP		0.53
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs779092501; hg19: chrX-67937375;