7-100487143-C-T

Variant names:

• chr7-100487143-C-T
• rs369137702
• NM_173564.4:c.391C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173564.4(NYAP1):​c.391C>T​(p.Pro131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P131T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: NYAP1 NM_173564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09604213).

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.391C>T	p.Pro131Ser	missense	Exon 3 of 7	NP_775835.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NYAP1	ENST00000300179.7	TSL:2 MANE Select	c.391C>T	p.Pro131Ser	missense	Exon 3 of 7	ENSP00000300179.2	Q6ZVC0-1
	NYAP1	ENST00000880488.1		c.391C>T	p.Pro131Ser	missense	Exon 3 of 7	ENSP00000550547.1
	NYAP1	ENST00000880489.1		c.391C>T	p.Pro131Ser	missense	Exon 2 of 6	ENSP00000550548.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384314 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 682308

African (AFR) AF: 0.00 AC: 0 AN: 29326

American (AMR) AF: 0.00 AC: 0 AN: 33326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21662

East Asian (EAS) AF: 0.00 AC: 0 AN: 36636

South Asian (SAS) AF: 0.00 AC: 0 AN: 75646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5414

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1074858

Other (OTH) AF: 0.00 AC: 0 AN: 56912

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.54
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.0010
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.047
Sift	Benign	0.63	T
Sift4G	Benign	0.78	T
Polyphen		0.74	P
Vest4		0.35
MutPred		0.27		Gain of phosphorylation at P131 (P = 0.0084)
MVP		0.082
MPC		0.21
ClinPred		0.13	T
GERP RS		1.0
PromoterAI		-0.036	Neutral
Varity_R		0.019
gMVP		0.037
Mutation Taster		=94/6	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: rs369137702; hg19: chr7-100084766;