Genetic Variant NYAP1:p.Ser51Leu (chr7-100486904-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173564.4(NYAP1):c.152C>T(p.Ser51Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,584,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

NYAP1
NM_173564.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

Publications

0 publications found

Variant links:

Genes affected

NYAP1 (HGNC:22009): (neuronal tyrosine phosphorylated phosphoinositide-3-kinase adaptor 1) Predicted to be involved in neuron projection morphogenesis and phosphatidylinositol 3-kinase signaling. [provided by Alliance of Genome Resources, Apr 2022]

NYAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173564.4. 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
	NYAP1	NM_173564.4	MANE Select	c.152C>T	p.Ser51Leu	missense	Exon 3 of 7	NP_775835.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NYAP1	ENST00000300179.7	TSL:2 MANE Select	c.152C>T	p.Ser51Leu	missense	Exon 3 of 7	ENSP00000300179.2	Q6ZVC0-1
NYAP1	ENST00000880488.1		c.152C>T	p.Ser51Leu	missense	Exon 3 of 7	ENSP00000550547.1
NYAP1	ENST00000880489.1		c.152C>T	p.Ser51Leu	missense	Exon 2 of 6	ENSP00000550548.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000208

AC:

AN:

192214

AF XY:

0.0000282

show subpopulations

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:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1432028

Hom.:

Cov.:

AF XY:

0.0000324

AC XY:

AN XY:

710534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32944

American (AMR)

AF:

0.00

AC:

AN:

40498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25488

East Asian (EAS)

AF:

0.00

AC:

AN:

38426

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5336

European-Non Finnish (NFE)

AF:

0.0000427

AC:

AN:

1099708

Other (OTH)

AF:

0.0000169

AC:

AN:

59288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000254

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.076

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.2

PhyloP100

4.9

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.1

REVEL

Benign

0.14

Sift

Benign

0.058

Sift4G

Benign

0.092

Polyphen

1.0

Vest4

0.71

MutPred

0.34

Loss of phosphorylation at S51 (P = 0.0199)

MVP

0.068

MPC

0.69

ClinPred

0.85

GERP RS

5.0

PromoterAI

0.0048

Neutral

(source)

Varity_R

0.29

gMVP

0.62

Mutation Taster

=50/50

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over