NM_000349.3:c.*966_*967dupAA

Variant names:

• chr8-38143305-A-ATT
• rs11326306
• NM_000349.3:c.*966_*967dupAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000349.3(STAR):​c.*966_*967dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0048 (9 hom., cov: 0)
• Consequence: STAR NM_000349.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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]

ASH2L (HGNC:744): (ASH2 like, histone lysine methyltransferase complex subunit) Enables beta-catenin binding activity and transcription cis-regulatory region binding activity. Contributes to histone methyltransferase activity (H3-K4 specific). Involved in histone H3-K4 methylation; positive regulation of cell population proliferation; and response to estrogen. Acts upstream of or within cellular response to DNA damage stimulus. Located in nucleus. Part of MLL3/4 complex and Set1C/COMPASS complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00477 (512/107240) while in subpopulation AFR AF= 0.0147 (441/30088). AF 95% confidence interval is 0.0135. There are 9 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAR	NM_000349.3	c.*966_*967dupAA		3_prime_UTR_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	c.*966_*967dupAA		3_prime_UTR_variant	Exon 7 of 7	1	NM_000349.3	ENSP00000276449.3
ASH2L	ENST00000521808.5	c.*5-416_*5-415dupTT		intron_variant	Intron 3 of 3	5		ENSP00000427839.1

Frequencies

GnomAD3 genomes AF: 0.00477 AC: 511 AN: 107222 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00363

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.000311

Gnomad FIN AF: 0.000867

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000184

Gnomad OTH AF: 0.00845

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00477 AC: 512 AN: 107240 Hom.: 9 Cov.: 0 AF XY: 0.00457 AC XY: 233 AN XY: 51028

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00177

Gnomad4 SAS AF: 0.000313

Gnomad4 FIN AF: 0.000867

Gnomad4 NFE AF: 0.000184

Gnomad4 OTH AF: 0.00844

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11326306; hg19: chr8-38000823;