chrX-68647907-T-A

Variant names:

• chrX-68647907-T-A
• rs2079525012
• NM_001142503.3:c.25T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142503.3(STARD8):​c.25T>A​(p.Ser9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000092 in 1,086,872 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 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. S9A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.518
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.105161935).

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.25T>A	p.Ser9Thr	missense	Exon 1 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_014725.5		c.-134T>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.25T>A	p.Ser9Thr	missense	Exon 1 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.-134T>A		5_prime_UTR	Exon 1 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000523864.5	TSL:1	n.25T>A		non_coding_transcript_exon	Exon 1 of 14	ENSP00000428031.1	E5RFN7

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.20e-7 AC: 1 AN: 1086872 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 355342

African (AFR) AF: 0.00 AC: 0 AN: 26114

American (AMR) AF: 0.00 AC: 0 AN: 33814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19139

East Asian (EAS) AF: 0.00 AC: 0 AN: 29650

South Asian (SAS) AF: 0.00 AC: 0 AN: 52040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39629

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 836659

Other (OTH) AF: 0.00 AC: 0 AN: 45707

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	15
DANN	Benign	0.95
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.52
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.068
Sift	Benign	0.47	T
Sift4G	Benign	0.16	T
Polyphen		0.012	B
Vest4		0.12
MutPred		0.67		Gain of sheet (P = 0.0477)
MVP		0.41
MPC		0.057
ClinPred		0.47	T
GERP RS		1.1
PromoterAI		0.024	Neutral
gMVP		0.12
Mutation Taster		=92/8	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: rs2079525012; hg19: chrX-67867749;