rs2004079

Positions:

• chr15-35085064-T-C
• chr15-35085064-T-G

Variant summary

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

The NM_001355281.2(NANOGP8):​c.47A>G​(p.Glu16Gly) 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. 8/11 in silico tools predict a benign outcome for this variant. 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. E16A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 28)
• Consequence: NANOGP8 NM_001355281.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

Genes affected

NANOGP8 (HGNC:23106): (Nanog homeobox retrogene P8) This gene represents a transcribed retrogene of the Nanog homeobox gene. The putative encoded protein may participate in reprogramming of cancer cells. In vitro studies using a recombinant protein have shown that the protein localizes to the nucleus and can promote cell proliferation, similar to the Nanog protein. [provided by RefSeq, Sep 2017]

LOC105370765 (HGNC:):

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=0.08089298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANOGP8	NM_001355281.2	c.47A>G	p.Glu16Gly	missense_variant	1/1	ENST00000528386.4
LOC105370765	XR_932103.4	n.19832-3869A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANOGP8	ENST00000528386.4	c.47A>G	p.Glu16Gly	missense_variant	1/1		NM_001355281.2	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.6
DANN	Benign	0.38
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.36	T;T
MetaRNN	Benign	0.081	T;T
Sift4G	Benign	0.19	T;T
Vest4		0.053
MVP		0.13
GERP RS		1.9
Varity_R		0.039
gMVP		0.23

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: rs2004079; hg19: chr15-35377265;