X-68647907-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001142503.3(STARD8):​c.25T>G​(p.Ser9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,086,872 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080284625).
• BP6: Variant X-68647907-T-G is Benign according to our data. Variant chrX-68647907-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3450325.Status of the report is criteria_provided_single_submitter, 1 stars.

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>G	p.Ser9Ala	missense	Exon 1 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_014725.5		c.-134T>G		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>G	p.Ser9Ala	missense	Exon 1 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.-134T>G		5_prime_UTR	Exon 1 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000523864.5	TSL:1	n.25T>G		non_coding_transcript_exon	Exon 1 of 14	ENSP00000428031.1	E5RFN7

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1086872 Hom.: 0 Cov.: 30 AF XY: 0.00000281 AC XY: 1 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: 0.0000219 AC: 1 AN: 45707

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.049
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	12
DANN	Benign	0.68
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.52
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.10
Sift	Benign	0.58	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.41
MPC		0.053
ClinPred		0.10	T
GERP RS		1.1
PromoterAI		-0.020	Neutral
gMVP		0.047
Mutation Taster		=93/7	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: rs2079525012; hg19: chrX-67867749;