NM_018671.5:c.2304-18C>T

Variant names:

• chr15-90952911-C-T
• rs1016389425
• NM_018671.5:c.2304-18C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_018671.5(UNC45A):​c.2304-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UNC45A NM_018671.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

UNC45A (HGNC:30594): (unc-45 myosin chaperone A) This gene encodes a regulatory component of the progesterone receptor/heat shock protein 90 chaperoning complex, which functions in the assembly and folding of the progesterone receptor. The encoded protein is thought to be essential for normal cell proliferation, and for the accumulation of myosin during development of muscle cells. [provided by RefSeq, Sep 2018]

RCCD1-AS1 (HGNC:54811): (RCCD1 and UNC45A antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-90952911-C-T is Benign according to our data. Variant chr15-90952911-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1958785.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018671.5. 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
	UNC45A	NM_018671.5	MANE Select	c.2304-18C>T		intron	N/A	NP_061141.2
	UNC45A	NM_001323619.1		c.2304-18C>T		intron	N/A	NP_001310548.1	Q9H3U1-1
	UNC45A	NM_001039675.2		c.2259-18C>T		intron	N/A	NP_001034764.1	Q9H3U1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC45A	ENST00000418476.2	TSL:1 MANE Select	c.2304-18C>T		intron	N/A	ENSP00000407487.2	Q9H3U1-1
	UNC45A	ENST00000639885.1	TSL:5	c.2724-18C>T		intron	N/A	ENSP00000491150.1	A0A1W2PNX8
	UNC45A	ENST00000936141.1		c.2391-18C>T		intron	N/A	ENSP00000606200.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454976 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724064

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108388

Other (OTH) AF: 0.00 AC: 0 AN: 60248

GnomAD4 genome Cov.: 32

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
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.78
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

Other links and lift over

dbSNP: rs1016389425; hg19: chr15-91496141;