rs6239

Positions:

• chr6-22287516-C-G
• chr6-22287516-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 16/21 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: 33)
• Consequence: PRL NM_000948.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029243857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRL	NM_000948.6	c.570G>C	p.Glu190Asp	missense_variant	5/5	ENST00000306482.2	NP_000939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000306482.2	c.570G>C	p.Glu190Asp	missense_variant	5/5	1	NM_000948.6	ENSP00000302150.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.029	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-0.82	.;.;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.86	.;.;N
REVEL	Benign	0.17
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;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

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: rs6239; hg19: chr6-22287745;