NM_018671.5:c.44C>G

Variant names:

• chr15-90935368-C-G
• rs370654049
• NM_018671.5:c.44C>G

Variant summary

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

The NM_018671.5(UNC45A):​c.44C>G​(p.Thr15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T15I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UNC45A NM_018671.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.81
• 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]

HDDC3 (HGNC:30522): (HD domain containing 3) Predicted to enable guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044869423).

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.44C>G	p.Thr15Ser	missense	Exon 1 of 20	NP_061141.2
	UNC45A	NM_001323619.1		c.44C>G	p.Thr15Ser	missense	Exon 2 of 21	NP_001310548.1	Q9H3U1-1
	UNC45A	NM_001323620.2		c.-540C>G		5_prime_UTR	Exon 1 of 20	NP_001310549.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC45A	ENST00000418476.2	TSL:1 MANE Select	c.44C>G	p.Thr15Ser	missense	Exon 1 of 20	ENSP00000407487.2	Q9H3U1-1
	UNC45A	ENST00000936141.1		c.44C>G	p.Thr15Ser	missense	Exon 1 of 21	ENSP00000606200.1
	UNC45A	ENST00000895398.1		c.44C>G	p.Thr15Ser	missense	Exon 1 of 20	ENSP00000565457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.11
DANN	Benign	0.57
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.089	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.8
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.027
Sift	Benign	0.39	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.20		Loss of helix (P = 0.1299)
MVP		0.19
MPC		0.11
ClinPred		0.055	T
GERP RS		-8.1
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.077
gMVP		0.12

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: rs370654049; hg19: chr15-91478598;