chr15-35085064-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355281.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOGP8	NM_001355281.2	MANE Select	c.47A>C	p.Glu16Ala	missense	Exon 1 of 1	NP_001342210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOGP8	ENST00000528386.4	TSL:6 MANE Select	c.47A>C	p.Glu16Ala	missense	Exon 1 of 1	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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.757 AC: 24298 AN: 32114

American (AMR) AF: 0.734 AC: 32684 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 18181 AN: 25642

East Asian (EAS) AF: 0.656 AC: 25788 AN: 39296

South Asian (SAS) AF: 0.756 AC: 64026 AN: 84658

European-Finnish (FIN) AF: 0.762 AC: 40045 AN: 52518

Middle Eastern (MID) AF: 0.764 AC: 3052 AN: 3994

European-Non Finnish (NFE) AF: 0.758 AC: 792765 AN: 1046136

Other (OTH) AF: 0.746 AC: 43081 AN: 57786

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.756 AC: 31131 AN: 41186

American (AMR) AF: 0.743 AC: 11270 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2424 AN: 3462

East Asian (EAS) AF: 0.669 AC: 3429 AN: 5124

South Asian (SAS) AF: 0.737 AC: 3505 AN: 4754

European-Finnish (FIN) AF: 0.757 AC: 7941 AN: 10490

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51025 AN: 67874

Other (OTH) AF: 0.756 AC: 1573 AN: 2082

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 v4.9

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
MetaRNN	Benign	0.0045	T
PhyloP100		-0.49
Sift4G	Benign	0.86	T
Vest4		0.044
MVP		0.048
GERP RS		1.9
PromoterAI		0.0074	Neutral
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

Other links and lift over

dbSNP: rs2004079; hg19: chr15-35377265; COSMIC: COSV71843668; COSMIC: COSV71843668;