chrX-68715299-T-C

Variant names:

• chrX-68715299-T-C
• NM_001142503.3:c.157T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142503.3(STARD8):​c.157T>C​(p.Ser53Pro) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.591
• 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=0.06769639).

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.157T>C	p.Ser53Pro	missense	Exon 4 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_001142504.3		c.-84T>C		5_prime_UTR	Exon 3 of 14	NP_001135976.1	Q92502-1
	STARD8	NM_014725.5		c.-7-1069T>C		intron	N/A	NP_055540.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD8	ENST00000374599.8	TSL:1 MANE Select	c.157T>C	p.Ser53Pro	missense	Exon 4 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000374597.3	TSL:1	c.-84T>C		5_prime_UTR	Exon 3 of 14	ENSP00000363725.3	Q92502-1
	STARD8	ENST00000252336.10	TSL:1	c.-7-1069T>C		intron	N/A	ENSP00000252336.6	Q92502-1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 24

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	Uncertain	0.35
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	15
DANN	Uncertain	0.98
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.59
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.077
Sift	Benign	0.18	T
Sift4G	Benign	0.30	T
Polyphen		0.26	B
Vest4		0.39
MutPred		0.32		Gain of sheet (P = 0.1208)
MVP		0.42
MPC		0.14
ClinPred		0.26	T
GERP RS		0.31
gMVP		0.34
Mutation Taster		=90/10	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

hg19: chrX-67935141;