12-7789729-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024865.4(NANOG):​c.115C>A​(p.Gln39Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

NANOG
NM_024865.4 missense

Scores

4
15

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.18
Variant links:
Genes affected
NANOG (HGNC:20857): (Nanog homeobox) The protein encoded by this gene is a DNA binding homeobox transcription factor involved in embryonic stem (ES) cell proliferation, renewal, and pluripotency. The encoded protein can block ES cell differentiation and can also autorepress its own expression in differentiating cells. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.005078733).
BP6
Variant 12-7789729-C-A is Benign according to our data. Variant chr12-7789729-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 749028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 115 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NANOGNM_024865.4 linkc.115C>A p.Gln39Lys missense_variant Exon 1 of 4 ENST00000229307.9 NP_079141.2 Q9H9S0-1A8K4D1
NANOGNM_001297698.2 linkc.115C>A p.Gln39Lys missense_variant Exon 1 of 4 NP_001284627.1 Q9H9S0-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NANOGENST00000229307.9 linkc.115C>A p.Gln39Lys missense_variant Exon 1 of 4 1 NM_024865.4 ENSP00000229307.4 Q9H9S0-1
NANOGENST00000526286.1 linkc.115C>A p.Gln39Lys missense_variant Exon 1 of 4 1 ENSP00000435288.1 Q9H9S0-2
NANOGENST00000541267.5 linkc.43C>A p.Gln15Lys missense_variant Exon 3 of 6 5 ENSP00000444434.1 F5GZI2
NANOGENST00000526434.2 linkn.297C>A non_coding_transcript_exon_variant Exon 1 of 2 4

Frequencies

GnomAD3 genomes
AF:
0.000756
AC:
115
AN:
152170
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00253
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000286
AC:
72
AN:
251452
Hom.:
0
AF XY:
0.000177
AC XY:
24
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00363
Gnomad AMR exome
AF:
0.000347
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000821
AC:
120
AN:
1461808
Hom.:
0
Cov.:
31
AF XY:
0.0000743
AC XY:
54
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00260
Gnomad4 AMR exome
AF:
0.000380
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.000755
AC:
115
AN:
152288
Hom.:
0
Cov.:
33
AF XY:
0.000685
AC XY:
51
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00253
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000524
Hom.:
0
Bravo
AF:
0.000948
ESP6500AA
AF:
0.00454
AC:
20
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000371
AC:
45

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 26, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Uncertain
0.55
.;D;.
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.0051
T;T;T
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Uncertain
2.2
.;M;M
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.23
Sift
Uncertain
0.0050
D;D;D
Sift4G
Benign
0.32
T;T;T
Polyphen
0.91
.;P;.
Vest4
0.27, 0.52
MVP
0.80
MPC
1.6
ClinPred
0.042
T
GERP RS
3.2
Varity_R
0.21
gMVP
0.20

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.

Other links and lift over

dbSNP: rs140243232; hg19: chr12-7942325; API