NM_001355281.2:c.190G>T

Variant names:

• chr15-35084921-C-A
• rs2257251
• NM_001355281.2:c.190G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001355281.2(NANOGP8):​c.190G>T​(p.Asp64Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,605,964 control chromosomes in the GnomAD database, including 19,884 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (2006 hom., cov: 30)
  • Exomes 𝑓: 0.17 (17878 hom.)
• Consequence: NANOGP8 NM_001355281.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.0600
• Publications: 4 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=0.002385676).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOGP8	NM_001355281.2	MANE Select	c.190G>T	p.Asp64Tyr	missense	Exon 1 of 1	NP_001342210.1	Q6NSW7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOGP8	ENST00000528386.4	TSL:6 MANE Select	c.190G>T	p.Asp64Tyr	missense	Exon 1 of 1	ENSP00000487073.2	Q6NSW7

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24060 AN: 151964 Hom.: 2006 Cov.: 30

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0863

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.172 AC: 250175 AN: 1453882 Hom.: 17878 Cov.: 35 AF XY: 0.172 AC XY: 124429 AN XY: 723548

African (AFR) AF: 0.103 AC: 3448 AN: 33386

American (AMR) AF: 0.134 AC: 6005 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 2269 AN: 26112

East Asian (EAS) AF: 0.123 AC: 4871 AN: 39692

South Asian (SAS) AF: 0.183 AC: 15748 AN: 85990

European-Finnish (FIN) AF: 0.239 AC: 12715 AN: 53276

Middle Eastern (MID) AF: 0.0907 AC: 440 AN: 4852

European-Non Finnish (NFE) AF: 0.176 AC: 194786 AN: 1105782

Other (OTH) AF: 0.165 AC: 9893 AN: 60108

GnomAD4 genome AF: 0.158 AC: 24073 AN: 152082 Hom.: 2006 Cov.: 30 AF XY: 0.162 AC XY: 12014 AN XY: 74326

African (AFR) AF: 0.107 AC: 4447 AN: 41506

American (AMR) AF: 0.161 AC: 2464 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0863 AC: 299 AN: 3464

East Asian (EAS) AF: 0.154 AC: 796 AN: 5172

South Asian (SAS) AF: 0.197 AC: 947 AN: 4808

European-Finnish (FIN) AF: 0.249 AC: 2629 AN: 10568

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11945 AN: 67970

Other (OTH) AF: 0.158 AC: 334 AN: 2114

Alfa AF: 0.163 Hom.: 256

Bravo AF: 0.148

Asia WGS AF: 0.196 AC: 680 AN: 3476

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Keratoconus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.92	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.4
DANN	Benign	0.71
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.00017	N
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0024	T
PhyloP100		0.060
Sift4G	Benign	0.14	T
Vest4		0.089
MVP		0.37
GERP RS		-0.46
PromoterAI		-0.0016	Neutral
Varity_R		0.044
gMVP		0.32

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: rs2257251; hg19: chr15-35377122; COSMIC: COSV71843588; COSMIC: COSV71843588;