X-68717235-G-T

Variant names:

• chrX-68717235-G-T
• rs375613703
• NM_001142503.3:c.321G>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.321G>T​(p.Glu107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,198,501 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000021 (0 hom. 3 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.173
• 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=0.026722133).
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.321G>T	p.Glu107Asp	missense	Exon 6 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_001142504.3		c.81G>T	p.Glu27Asp	missense	Exon 5 of 14	NP_001135976.1	Q92502-1
	STARD8	NM_014725.5		c.81G>T	p.Glu27Asp	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.321G>T	p.Glu107Asp	missense	Exon 6 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.81G>T	p.Glu27Asp	missense	Exon 5 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000374597.3	TSL:1	c.81G>T	p.Glu27Asp	missense	Exon 5 of 14	ENSP00000363725.3	Q92502-1

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111753 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000126 AC: 2 AN: 158515 AF XY: 0.0000213

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000289

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 23 AN: 1086748 Hom.: 0 Cov.: 31 AF XY: 0.00000847 AC XY: 3 AN XY: 354108

African (AFR) AF: 0.00 AC: 0 AN: 26207

American (AMR) AF: 0.00 AC: 0 AN: 34031

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18897

East Asian (EAS) AF: 0.00 AC: 0 AN: 29987

South Asian (SAS) AF: 0.00 AC: 0 AN: 51957

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.0000251 AC: 21 AN: 836123

Other (OTH) AF: 0.0000438 AC: 2 AN: 45640

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111753 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33941

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30660

American (AMR) AF: 0.00 AC: 0 AN: 10637

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3536

South Asian (SAS) AF: 0.00 AC: 0 AN: 2579

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6169

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53104

Other (OTH) AF: 0.00 AC: 0 AN: 1507

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00000826 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.19
DEOGEN2	Benign	0.0090	T
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.17
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.94	N
REVEL	Benign	0.076
Sift	Benign	0.87	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.35		Gain of loop (P = 0.0097)
MVP		0.16
MPC		0.14
ClinPred		0.044	T
GERP RS		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.064
gMVP		0.036
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs375613703; hg19: chrX-67937077;