Genetic Variant NANOGP8:p.Glu16Ala (chr15-35085064-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.488

Publications

5 publications found

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 was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANOGP8	NM_001355281.2 link	c.47A>C	p.Glu16Ala	missense_variant	Exon 1 of 1	ENST00000528386.4	NP_001342210.1
LOC105370765	XR_932103.4 link	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 link	c.47A>C	p.Glu16Ala	missense_variant	Exon 1 of 1	6	NM_001355281.2	ENSP00000487073.2		Q6NSW7

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113271

AN:

151234

Hom.:

42512

Cov.:

show subpopulations

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.:

AF XY:

0.753

AC XY:

521916

AN XY:

692740

show subpopulations

⚠️ 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 = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.391

Heterozygous variant carriers

8550

17100

25650

34200

42750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18672

37344

56016

74688

93360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.749

AC:

113366

AN:

151350

Hom.:

42550

Cov.:

AF XY:

0.749

AC XY:

55337

AN XY:

73922

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1231

2463

3694

4926

6157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.48

(source)

DANN

Benign

0.38

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.0045

T;T

PhyloP100

-0.49

Sift4G

Benign

0.86

T;T

Vest4

0.044

MVP

0.048

GERP RS

1.9

PromoterAI

0.0074

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over