X-68647887-C-A

Variant names:

• chrX-68647887-C-A
• rs368190357
• NM_001142503.3:c.5C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142503.3(STARD8):​c.5C>A​(p.Pro2His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.376374).

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.5C>A	p.Pro2His	missense	Exon 1 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_014725.5		c.-154C>A		5_prime_UTR	Exon 1 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.5C>A	p.Pro2His	missense	Exon 1 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.-154C>A		5_prime_UTR	Exon 1 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000523864.5	TSL:1	n.5C>A		non_coding_transcript_exon	Exon 1 of 14	ENSP00000428031.1	E5RFN7

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1085488 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 354730

African (AFR) AF: 0.00 AC: 0 AN: 26077

American (AMR) AF: 0.00 AC: 0 AN: 33615

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19106

East Asian (EAS) AF: 0.00 AC: 0 AN: 29535

South Asian (SAS) AF: 0.00 AC: 0 AN: 51926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39487

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 835966

Other (OTH) AF: 0.00 AC: 0 AN: 45660

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Uncertain	26
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.2	T
PhyloP100		2.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.38		Loss of catalytic residue at P2 (P = 0.0013)
MVP		0.26
MPC		0.13
ClinPred		0.99	D
GERP RS		4.1
PromoterAI		-0.16	Neutral
gMVP		0.25
Mutation Taster		=295/5	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: rs368190357; hg19: chrX-67867729;