15-90953020-A-C

Variant names:

• chr15-90953020-A-C
• rs966732163
• NM_018671.5:c.2395A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018671.5(UNC45A):​c.2395A>C​(p.Met799Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M799V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UNC45A NM_018671.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.46
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2395A>C	p.Met799Leu	missense	Exon 18 of 20	NP_061141.2
	UNC45A	NM_001323619.1		c.2395A>C	p.Met799Leu	missense	Exon 19 of 21	NP_001310548.1	Q9H3U1-1
	UNC45A	NM_001039675.2		c.2350A>C	p.Met784Leu	missense	Exon 21 of 23	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.2395A>C	p.Met799Leu	missense	Exon 18 of 20	ENSP00000407487.2	Q9H3U1-1
	UNC45A	ENST00000639885.1	TSL:5	c.2815A>C	p.Met939Leu	missense	Exon 20 of 22	ENSP00000491150.1	A0A1W2PNX8
	UNC45A	ENST00000936141.1		c.2482A>C	p.Met828Leu	missense	Exon 19 of 21	ENSP00000606200.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Benign	0.24	T
Sift4G	Benign	0.18	T
Polyphen		0.70	P
Vest4		0.74
MutPred		0.50		Gain of helix (P = 0.2294)
MVP		0.44
MPC		0.16
ClinPred		0.71	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.45

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: rs966732163; hg19: chr15-91496250;