chr17-4676115-C-T

Variant names:

• chr17-4676115-C-T
• NM_014389.3:c.901G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_014389.3(PELP1):​c.901G>A​(p.Glu301Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PELP1 NM_014389.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

PELP1 (HGNC:30134): (proline, glutamate and leucine rich protein 1) This gene encodes a transcription factor which coactivates transcription of estrogen receptor responsive genes and corepresses genes activated by other hormone receptors or sequence-specific transcription factors. Expression of this gene is regulated by both members of the estrogen receptor family. This gene may be involved in the progression of several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ENSG00000235085 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-4676115-C-T is Benign according to our data. Variant chr17-4676115-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3211387.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PELP1	NM_014389.3	c.901G>A	p.Glu301Lys	missense_variant	Exon 8 of 17	ENST00000572293.7	NP_055204.4
PELP1	NM_001278241.2	c.460G>A	p.Glu154Lys	missense_variant	Exon 9 of 19		NP_001265170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PELP1	ENST00000572293.7	c.901G>A	p.Glu301Lys	missense_variant	Exon 8 of 17	1	NM_014389.3	ENSP00000460300.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 12, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;T;T;T
Eigen	Benign	0.075
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	.;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	.;L;.;.
PhyloP100		3.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	.;.;.;N
REVEL	Benign	0.044
Sift	Benign	0.16	.;.;.;T
Sift4G	Benign	0.062	T;T;T;D
Polyphen		0.32, 0.18	.;B;.;B
Vest4		0.35
MutPred		0.37		.;Loss of stability (P = 0.0071);.;.;
MVP		0.32
MPC		0.41
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: 47

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-4579410;