19-45914464-G-C

Variant names:

• chr19-45914464-G-C
• rs143135004
• NM_001029861.3:c.230C>G

Variant summary

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

The NM_001029861.3(NANOS2):​c.230C>G​(p.Ser77Cys) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NANOS2 NM_001029861.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• Publications: 1 publications found

Genes affected

NANOS2 (HGNC:23292): (nanos C2HC-type zinc finger 2) Predicted to enable mRNA binding activity. Involved in negative regulation of translation and positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay. Located in nucleus and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.33793437).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029861.3. 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
	NANOS2	NM_001029861.3	MANE Select	c.230C>G	p.Ser77Cys	missense	Exon 1 of 1	NP_001025032.1	P60321

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOS2	ENST00000341294.4	TSL:6 MANE Select	c.230C>G	p.Ser77Cys	missense	Exon 1 of 1	ENSP00000341021.2	P60321

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.099
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.1
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Benign	0.075	T
Sift4G	Benign	0.070	T
Polyphen		0.93	P
Vest4		0.22
MutPred		0.29		Loss of disorder (P = 0.0014)
MVP		0.19
MPC		1.2
ClinPred		0.93	D
GERP RS		4.7
PromoterAI		0.0057	Neutral
Varity_R		0.12
gMVP		0.59
Mutation Taster		=79/21	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

dbSNP: rs143135004; hg19: chr19-46417722;