Genetic Variant NANOGP8:p.Asp64Tyr (chr15-35084921-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2006 hom., cov: 30)

Exomes 𝑓: 0.17 ( 17878 hom. )

Consequence

NANOGP8
NM_001355281.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.0600

Variant links:

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]

NANOGP8 links:

LOC105370765 (HGNC:):

LOC105370765 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANOGP8	NM_001355281.2 link	c.190G>T	p.Asp64Tyr	missense_variant	Exon 1 of 1	ENST00000528386.4	NP_001342210.1
LOC105370765	XR_932103.4 link	n.19832-3726G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NANOGP8	ENST00000528386.4 link	c.190G>T	p.Asp64Tyr	missense_variant	Exon 1 of 1	6	NM_001355281.2	ENSP00000487073.2		Q6NSW7

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24060

AN:

151964

Hom.:

2006

Cov.:

show subpopulations

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.:

AF XY:

0.172

AC XY:

124429

AN XY:

723548

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.0869

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.158

AC:

24073

AN:

152082

Hom.:

2006

Cov.:

AF XY:

0.162

AC XY:

12014

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.0863

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.166

Hom.:

250

Bravo

AF:

0.148

Asia WGS

AF:

0.196

AC:

680

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Keratoconus

Uncertain:1

Apr 01, 2023

Institute of Human Genetics, Polish Academy of Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.92

BayesDel_noAF

Benign

-0.94

CADD

Benign

8.4

DANN

Benign

0.71

DEOGEN2

Benign

0.16

T;.

FATHMM_MKL

Benign

0.00017

LIST_S2

Benign

0.83

T;D

MetaRNN

Benign

0.0024

T;T

Sift4G

Benign

0.14

T;T

Vest4

0.089

MVP

0.37

GERP RS

-0.46

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over