NM_000948.6:c.570G>C

Variant names:

• chr6-22287516-C-G
• rs6239
• NM_000948.6:c.570G>C

Variant summary

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

The NM_000948.6(PRL):​c.570G>C​(p.Glu190Asp) 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. 17/22 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: 33)
• Consequence: PRL NM_000948.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 14 publications found

Genes affected

PRL (HGNC:9445): (prolactin) This gene encodes the anterior pituitary hormone prolactin. This secreted hormone is a growth regulator for many tissues, including cells of the immune system. It may also play a role in cell survival by suppressing apoptosis, and it is essential for lactation. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011]

CASC15 (HGNC:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [provided by RefSeq, Dec 2017]

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=0.029243857).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000948.6. 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
	PRL	NM_000948.6	MANE Select	c.570G>C	p.Glu190Asp	missense	Exon 5 of 5	NP_000939.1	Q5THQ0
	PRL	NM_001163558.3		c.570G>C	p.Glu190Asp	missense	Exon 6 of 6	NP_001157030.1	Q5THQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRL	ENST00000306482.2	TSL:1 MANE Select	c.570G>C	p.Glu190Asp	missense	Exon 5 of 5	ENSP00000302150.1	P01236
	PRL	ENST00000617911.4	TSL:1	c.573G>C	p.Glu191Asp	missense	Exon 5 of 5	ENSP00000480195.1	Q5I0G2
	PRL	ENST00000651757.1		c.390G>C	p.Glu130Asp	missense	Exon 5 of 5	ENSP00000499154.1	A0A494C1P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.050
DANN	Benign	0.79
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-0.82	N
PhyloP100		-0.76
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.86	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.46		Gain of helix (P = 0.132)
MVP		0.67
MPC		0.38
ClinPred		0.061	T
GERP RS		-10
Varity_R		0.29
gMVP		0.093
Mutation Taster		=91/9	polymorphism

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: rs6239; hg19: chr6-22287745;