12-7795089-C-T

Variant names:

• chr12-7795089-C-T
• rs778880176
• NM_024865.4:c.912C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_024865.4(NANOG):​c.912C>T​(p.Asp304Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000668 in 149,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NANOG NM_024865.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.829
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-7795089-C-T is Benign according to our data. Variant chr12-7795089-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2642682.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.829 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.912C>T	p.Asp304Asp	synonymous	Exon 4 of 4	NP_079141.2	Q9H9S0-1
	NANOG	NM_001297698.2		c.864C>T	p.Asp288Asp	synonymous	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.912C>T	p.Asp304Asp	synonymous	Exon 4 of 4	ENSP00000229307.4	Q9H9S0-1
	NANOG	ENST00000526286.1	TSL:1	c.864C>T	p.Asp288Asp	synonymous	Exon 4 of 4	ENSP00000435288.1	Q9H9S0-2
	NANOG	ENST00000933164.1		c.912C>T	p.Asp304Asp	synonymous	Exon 5 of 5	ENSP00000603223.1

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149760 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000261 AC: 4 AN: 153480 AF XY: 0.0000480

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000515

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000208 AC: 23 AN: 1105188 Hom.: 0 Cov.: 15 AF XY: 0.0000212 AC XY: 12 AN XY: 566760

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26274

American (AMR) AF: 0.00 AC: 0 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24012

East Asian (EAS) AF: 0.00 AC: 0 AN: 38328

South Asian (SAS) AF: 0.00 AC: 0 AN: 79394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3480

European-Non Finnish (NFE) AF: 0.0000287 AC: 23 AN: 802420

Other (OTH) AF: 0.00 AC: 0 AN: 49090

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149760 Hom.: 0 Cov.: 29 AF XY: 0.0000137 AC XY: 1 AN XY: 73172

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40102

American (AMR) AF: 0.00 AC: 0 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67388

Other (OTH) AF: 0.00 AC: 0 AN: 2046

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.83
PhyloP100		-0.83

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

dbSNP: rs778880176; hg19: chr12-7947685;