chr15-90974159-T-G

Variant names:

• chr15-90974159-T-G
• rs2038441963
• NM_003981.4:c.1438A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003981.4(PRC1):​c.1438A>C​(p.Asn480His) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRC1 NM_003981.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

Genes affected

PRC1 (HGNC:9341): (protein regulator of cytokinesis 1) This gene encodes a protein that is involved in cytokinesis. The protein is present at high levels during the S and G2/M phases of mitosis but its levels drop dramatically when the cell exits mitosis and enters the G1 phase. It is located in the nucleus during interphase, becomes associated with mitotic spindles in a highly dynamic manner during mitosis, and localizes to the cell mid-body during cytokinesis. This protein has been shown to be a substrate of several cyclin-dependent kinases (CDKs). It is necessary for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ENSG00000284946 (HGNC:):

PRC1-AS1 (HGNC:48587): (PRC1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073857784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRC1	NM_003981.4	c.1438A>C	p.Asn480His	missense_variant	Exon 11 of 15	ENST00000394249.8	NP_003972.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRC1	ENST00000394249.8	c.1438A>C	p.Asn480His	missense_variant	Exon 11 of 15	1	NM_003981.4	ENSP00000377793.3
ENSG00000284946	ENST00000643536.1	n.*1401A>C		non_coding_transcript_exon_variant	Exon 32 of 35			ENSP00000494429.1
ENSG00000284946	ENST00000643536.1	n.*1401A>C		3_prime_UTR_variant	Exon 32 of 35			ENSP00000494429.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.6
DANN	Benign	0.88
DEOGEN2	Benign	0.055	T;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.048
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.21
MutPred		0.40		Gain of ubiquitination at K484 (P = 0.1103);Gain of ubiquitination at K484 (P = 0.1103);.;
MVP		0.28
MPC		0.078
ClinPred		0.034	T
GERP RS		1.9
Varity_R		0.042
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs2038441963; hg19: chr15-91517389;