rs104894087

Variant names:

• chr8-38144382-C-G
• NM_000349.3:c.749G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-38144382-C-G
• chr8-38144382-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_000349.3(STAR):​c.749G>C​(p.Trp250Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,442,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: STAR NM_000349.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.28

Genes affected

STAR (HGNC:11359): (steroidogenic acute regulatory protein) The protein encoded by this gene plays a key role in the acute regulation of steroid hormone synthesis by enhancing the conversion of cholesterol into pregnenolone. This protein permits the cleavage of cholesterol into pregnenolone by mediating the transport of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane. Mutations in this gene are a cause of congenital lipoid adrenal hyperplasia (CLAH), also called lipoid CAH. A pseudogene of this gene is located on chromosome 13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a chain Steroidogenic acute regulatory protein, mitochondrial (size 221) in uniprot entity STAR_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in NM_000349.3
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAR	NM_000349.3	c.749G>C	p.Trp250Ser	missense_variant	Exon 7 of 7	ENST00000276449.9	NP_000340.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAR	ENST00000276449.9	c.749G>C	p.Trp250Ser	missense_variant	Exon 7 of 7	1	NM_000349.3	ENSP00000276449.3
STAR	ENST00000522050.1	c.589G>C	p.Gly197Arg	missense_variant	Exon 5 of 5	5		ENSP00000429009.1
STAR	ENST00000520114.1	n.2718G>C		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1442378 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2 AN XY: 715570

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000363

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.44	B
Vest4		0.86
MutPred		0.79		Gain of disorder (P = 0.0095);
MVP		0.89
MPC		0.63
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.98
gMVP		0.86

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-38001900;