NM_001142503.3:c.653G>A

Variant names:

• chrX-68717567-G-A
• rs377275769
• NM_001142503.3:c.653G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001142503.3(STARD8):​c.653G>A​(p.Arg218Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000562 in 1,210,058 control chromosomes in the GnomAD database, including 1 homozygotes. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R218W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000061 (1 hom. 19 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.70
• Publications: 1 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=0.1127657).
• BP6: Variant X-68717567-G-A is Benign according to our data. Variant chrX-68717567-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2660785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 19 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.653G>A	p.Arg218Gln	missense	Exon 6 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_001142504.3		c.413G>A	p.Arg138Gln	missense	Exon 5 of 14	NP_001135976.1	Q92502-1
	STARD8	NM_014725.5		c.413G>A	p.Arg138Gln	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.653G>A	p.Arg218Gln	missense	Exon 6 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.413G>A	p.Arg138Gln	missense	Exon 5 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000374597.3	TSL:1	c.413G>A	p.Arg138Gln	missense	Exon 5 of 14	ENSP00000363725.3	Q92502-1

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112080 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000656 AC: 12 AN: 182856 AF XY: 0.0000445

Gnomad AFR exome AF: 0.0000761

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000144

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000856

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000610 AC: 67 AN: 1097978 Hom.: 1 Cov.: 33 AF XY: 0.0000523 AC XY: 19 AN XY: 363390

African (AFR) AF: 0.000114 AC: 3 AN: 26402

American (AMR) AF: 0.000114 AC: 4 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.000132 AC: 4 AN: 30205

South Asian (SAS) AF: 0.0000739 AC: 4 AN: 54141

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.0000558 AC: 47 AN: 842134

Other (OTH) AF: 0.000108 AC: 5 AN: 46095

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112080 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34236

African (AFR) AF: 0.0000324 AC: 1 AN: 30841

American (AMR) AF: 0.00 AC: 0 AN: 10678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3539

South Asian (SAS) AF: 0.00 AC: 0 AN: 2660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6109

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53169

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	17
DANN	Benign	0.67
DEOGEN2	Benign	0.047	T
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.7
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.022
Sift	Benign	0.57	T
Sift4G	Benign	0.62	T
Polyphen		0.35	B
Vest4		0.12
MVP		0.70
MPC		0.12
ClinPred		0.046	T
GERP RS		3.5
Varity_R		0.10
gMVP		0.45
Mutation Taster		=97/3	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: rs377275769; hg19: chrX-67937409; COSMIC: COSV52927584;