X-68717464-C-T

Variant names:

• chrX-68717464-C-T
• rs199792176
• NM_001142503.3:c.550C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001142503.3(STARD8):​c.550C>T​(p.Arg184Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 1,208,115 control chromosomes in the GnomAD database, including 1 homozygotes. There are 129 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., 12 hem., cov: 22)
  • Exomes 𝑓: 0.00035 (1 hom. 117 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.820
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02575615).
• BS2: High Hemizygotes in GnomAd4 at 12 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.550C>T	p.Arg184Trp	missense	Exon 6 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_001142504.3		c.310C>T	p.Arg104Trp	missense	Exon 5 of 14	NP_001135976.1	Q92502-1
	STARD8	NM_014725.5		c.310C>T	p.Arg104Trp	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.550C>T	p.Arg184Trp	missense	Exon 6 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.310C>T	p.Arg104Trp	missense	Exon 5 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000374597.3	TSL:1	c.310C>T	p.Arg104Trp	missense	Exon 5 of 14	ENSP00000363725.3	Q92502-1

Frequencies

GnomAD3 genomes AF: 0.000369 AC: 41 AN: 111211 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000983

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000472

Gnomad OTH AF: 0.000664

GnomAD2 exomes AF: 0.000216 AC: 39 AN: 180769 AF XY: 0.000167

Gnomad AFR exome AF: 0.0000767

Gnomad AMR exome AF: 0.000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.000669

GnomAD4 exome AF: 0.000351 AC: 385 AN: 1096850 Hom.: 1 Cov.: 33 AF XY: 0.000323 AC XY: 117 AN XY: 362454

African (AFR) AF: 0.000114 AC: 3 AN: 26400

American (AMR) AF: 0.000341 AC: 12 AN: 35167

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19351

East Asian (EAS) AF: 0.00 AC: 0 AN: 30194

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39653

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.000424 AC: 357 AN: 841811

Other (OTH) AF: 0.000261 AC: 12 AN: 46052

GnomAD4 genome AF: 0.000368 AC: 41 AN: 111265 Hom.: 0 Cov.: 22 AF XY: 0.000358 AC XY: 12 AN XY: 33479

African (AFR) AF: 0.0000981 AC: 3 AN: 30595

American (AMR) AF: 0.00113 AC: 12 AN: 10574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3505

South Asian (SAS) AF: 0.00 AC: 0 AN: 2553

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5989

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000472 AC: 25 AN: 52980

Other (OTH) AF: 0.000655 AC: 1 AN: 1526

Alfa AF: 0.00485 Hom.: 6

Bravo AF: 0.000351

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.000189 AC: 23

EpiCase AF: 0.000273

EpiControl AF: 0.000416

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	0.064
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.83	L
PhyloP100		0.82
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.032
Sift	Benign	0.074	T
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.064
MVP		0.73
MPC		0.064
ClinPred		0.029	T
GERP RS		1.3
Varity_R		0.083
gMVP		0.21
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs199792176; hg19: chrX-67937306;