chr12-7794821-C-A

Variant names:

• chr12-7794821-C-A
• NM_024865.4:c.644C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024865.4(NANOG):​c.644C>A​(p.Ser215Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S215A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 25)
• Consequence: NANOG NM_024865.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28047428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024865.4. 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
	NANOG	NM_024865.4	MANE Select	c.644C>A	p.Ser215Tyr	missense	Exon 4 of 4	NP_079141.2	Q9H9S0-1
	NANOG	NM_001297698.2		c.596C>A	p.Ser199Tyr	missense	Exon 4 of 4	NP_001284627.1	Q9H9S0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOG	ENST00000229307.9	TSL:1 MANE Select	c.644C>A	p.Ser215Tyr	missense	Exon 4 of 4	ENSP00000229307.4	Q9H9S0-1
	NANOG	ENST00000526286.1	TSL:1	c.596C>A	p.Ser199Tyr	missense	Exon 4 of 4	ENSP00000435288.1	Q9H9S0-2
	NANOG	ENST00000933164.1		c.644C>A	p.Ser215Tyr	missense	Exon 5 of 5	ENSP00000603223.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.0063	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		0.98	D
Vest4		0.26
MutPred		0.40		Loss of disorder (P = 0.0064)
MVP		0.81
MPC		2.1
ClinPred		0.94	D
GERP RS		2.2
Varity_R		0.15
gMVP		0.37
Mutation Taster		=99/1	polymorphism

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

hg19: chr12-7947417;