X-68717653-A-G

Variant names:

• chrX-68717653-A-G
• rs201848778
• NM_001142503.3:c.739A>G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001142503.3(STARD8):​c.739A>G​(p.Ser247Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,210,574 control chromosomes in the GnomAD database, including 2 homozygotes. There are 438 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., 58 hem., cov: 23)
  • Exomes 𝑓: 0.0010 (0 hom. 380 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.43

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

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032622218).
• BP6: Variant X-68717653-A-G is Benign according to our data. Variant chrX-68717653-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 711733.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD8	NM_001142503.3	c.739A>G	p.Ser247Gly	missense_variant	Exon 6 of 15	ENST00000374599.8	NP_001135975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD8	ENST00000374599.8	c.739A>G	p.Ser247Gly	missense_variant	Exon 6 of 15	1	NM_001142503.3	ENSP00000363727.3

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 181 AN: 112323 Hom.: 2 Cov.: 23 AF XY: 0.00168 AC XY: 58 AN XY: 34505

Gnomad AFR AF: 0.000226

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0000934

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000743 AC: 136 AN: 183086 Hom.: 0 AF XY: 0.000694 AC XY: 47 AN XY: 67756

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.000182

Gnomad ASJ exome AF: 0.00147

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00150

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.00104 AC: 1146 AN: 1098200 Hom.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 380 AN XY: 363568

Gnomad4 AFR exome AF: 0.000189

Gnomad4 AMR exome AF: 0.000170

Gnomad4 ASJ exome AF: 0.00211

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00119

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.000651

GnomAD4 genome AF: 0.00161 AC: 181 AN: 112374 Hom.: 2 Cov.: 23 AF XY: 0.00168 AC XY: 58 AN XY: 34566

Gnomad4 AFR AF: 0.000226

Gnomad4 AMR AF: 0.0000933

Gnomad4 ASJ AF: 0.00113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00129

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00141 Hom.: 59

Bravo AF: 0.00205

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00104 AC: 3

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000743 AC: 5

ExAC AF: 0.000684 AC: 83

EpiCase AF: 0.000981

EpiControl AF: 0.000949

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Apr 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.739A>G (p.S247G) alteration is located in exon 6 (coding exon 6) of the STARD8 gene. This alteration results from a A to G substitution at nucleotide position 739, causing the serine (S) at amino acid position 247 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1

Aug 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.0088	T;.;T
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.61	T;T;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L;.;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.090	N;N;N
REVEL	Benign	0.082
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.058
MVP		0.86
MPC		0.098
ClinPred		0.011	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs201848778; hg19: chrX-67937495;