7-25228393-G-C

Variant names:

• chr7-25228393-G-C
• rs569087357
• NM_022150.3:c.47C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_022150.3(NPVF):​c.47C>G​(p.Thr16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,583,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T16I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: NPVF NM_022150.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 4 publications found

Genes affected

NPVF (HGNC:13782): (neuropeptide VF precursor) Predicted to enable signaling receptor binding activity. Involved in negative regulation of gonadotropin secretion. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40950412).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022150.3. 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
	NPVF	NM_022150.3	MANE Select	c.47C>G	p.Thr16Ser	missense	Exon 1 of 3	NP_071433.3	Q9HCQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPVF	ENST00000222674.2	TSL:1 MANE Select	c.47C>G	p.Thr16Ser	missense	Exon 1 of 3	ENSP00000222674.2	Q9HCQ7-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152174 Hom.: 0 Cov.: 33

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: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 249252 AF XY: 0.0000297

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000140 AC: 20 AN: 1431062 Hom.: 0 Cov.: 27 AF XY: 0.0000182 AC XY: 13 AN XY: 713686

African (AFR) AF: 0.00 AC: 0 AN: 32846

American (AMR) AF: 0.00 AC: 0 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.00 AC: 0 AN: 39360

South Asian (SAS) AF: 0.000223 AC: 19 AN: 85134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085244

Other (OTH) AF: 0.0000169 AC: 1 AN: 59316

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000578 AC: 2 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.95
Eigen	Benign	0.13
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.76	T
PhyloP100		1.1
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.18
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.040	D
Vest4		0.39
MutPred		0.77		Loss of helix (P = 0.1299)
MVP		0.076
MPC		0.11
ClinPred		0.64	D
GERP RS		3.6
PromoterAI		0.0098	Neutral
gMVP		0.56
Mutation Taster		=83/17	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: rs569087357; hg19: chr7-25268012;