rs140506129

Variant names:

• chr6-22292638-C-A
• rs140506129
• NM_000948.6:c.212G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-22292638-C-A
• chr6-22292638-C-T

Variant summary

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

The NM_000948.6(PRL):​c.212G>T​(p.Arg71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,204 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R71Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PRL NM_000948.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 1 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: 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_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.212G>T	p.Arg71Leu	missense	Exon 3 of 5	NP_000939.1	Q5THQ0
	PRL	NM_001163558.3		c.212G>T	p.Arg71Leu	missense	Exon 4 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.212G>T	p.Arg71Leu	missense	Exon 3 of 5	ENSP00000302150.1	P01236
	PRL	ENST00000617911.4	TSL:1	c.215G>T	p.Arg72Leu	missense	Exon 3 of 5	ENSP00000480195.1	Q5I0G2
	PRL	ENST00000651757.1		c.212G>T	p.Arg71Leu	missense	Exon 4 of 5	ENSP00000499154.1	A0A494C1P2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249604 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460188 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726268

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 85998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111204

Other (OTH) AF: 0.0000332 AC: 2 AN: 60300

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152016 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74240

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	8.9
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.079	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.48
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.031	D
Polyphen		0.94	P
Vest4		0.52
MutPred		0.46		Loss of disorder (P = 0.0472)
MVP		0.86
MPC		1.0
ClinPred		0.93	D
GERP RS		-1.7
Varity_R		0.45
gMVP		0.31
Mutation Taster		=69/31	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: rs140506129; hg19: chr6-22292867; COSMIC: COSV100122990;