12-7794705-C-T

Variant names:

• chr12-7794705-C-T
• rs148350742
• NM_024865.4:c.528C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024865.4(NANOG):​c.528C>T​(p.Ser176Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NANOG NM_024865.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.475 with no splicing effect.

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.528C>T	p.Ser176Ser	synonymous	Exon 4 of 4	NP_079141.2	Q9H9S0-1
	NANOG	NM_001297698.2		c.502-22C>T		intron	N/A	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.528C>T	p.Ser176Ser	synonymous	Exon 4 of 4	ENSP00000229307.4	Q9H9S0-1
	NANOG	ENST00000526286.1	TSL:1	c.502-22C>T		intron	N/A	ENSP00000435288.1	Q9H9S0-2
	NANOG	ENST00000933164.1		c.528C>T	p.Ser176Ser	synonymous	Exon 5 of 5	ENSP00000603223.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241656 AF XY: 0.00000766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448668 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 719596

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.00 AC: 0 AN: 42580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24778

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 83522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106514

Other (OTH) AF: 0.00 AC: 0 AN: 59810

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.70
PhyloP100		-0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs148350742; hg19: chr12-7947301;