15-35085064-T-G

Variant names:

• chr15-35085064-T-G
• rs2004079
• NM_001355281.2:c.47A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001355281.2(NANOGP8):​c.47A>C​(p.Glu16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,538,028 control chromosomes in the GnomAD database, including 438,632 homozygotes. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.75 (42550 hom., cov: 28)
  • Exomes 𝑓: 0.75 (396082 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044605136).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANOGP8	NM_001355281.2	c.47A>C	p.Glu16Ala	missense_variant	Exon 1 of 1	ENST00000528386.4	NP_001342210.1
LOC105370765	XR_932103.4	n.19832-3869A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NANOGP8	ENST00000528386.4	c.47A>C	p.Glu16Ala	missense_variant	Exon 1 of 1	6	NM_001355281.2	ENSP00000487073.2

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113271 AN: 151234 Hom.: 42512 Cov.: 28

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.752

GnomAD4 exome AF: 0.753 AC: 1043920 AN: 1386678 Hom.: 396082 Cov.: 32 AF XY: 0.753 AC XY: 521916 AN XY: 692740

Gnomad4 AFR exome AF: 0.757

Gnomad4 AMR exome AF: 0.734

Gnomad4 ASJ exome AF: 0.709

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.756

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.758

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.749 AC: 113366 AN: 151350 Hom.: 42550 Cov.: 28 AF XY: 0.749 AC XY: 55337 AN XY: 73922

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.756

Alfa AF: 0.747 Hom.: 5256

Bravo AF: 0.747

Asia WGS AF: 0.718 AC: 2496 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.96	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.38
FATHMM_MKL	Benign	0.00014	N
LIST_S2	Benign	0.26	T;T
MetaRNN	Benign	0.0045	T;T
Sift4G	Benign	0.86	T;T
Vest4		0.044
MVP		0.048
GERP RS		1.9
Varity_R		0.038
gMVP		0.24

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; COSMIC: COSV71843668; COSMIC: COSV71843668;