7-100488266-C-G

Variant names:

• chr7-100488266-C-G
• rs202194930
• NM_173564.4:c.545C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173564.4(NYAP1):​c.545C>G​(p.Pro182Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P182L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NYAP1 NM_173564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056560665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NYAP1	NM_173564.4	c.545C>G	p.Pro182Arg	missense_variant	Exon 4 of 7	ENST00000300179.7	NP_775835.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NYAP1	ENST00000300179.7	c.545C>G	p.Pro182Arg	missense_variant	Exon 4 of 7	2	NM_173564.4	ENSP00000300179.2
NYAP1	ENST00000454988.1	c.374C>G	p.Pro125Arg	missense_variant	Exon 2 of 5	5		ENSP00000394424.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461630 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.76
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.24	N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.054
Sift	Benign	0.38	T;T
Sift4G	Benign	0.90	T;T
Polyphen		0.37	B;.
Vest4		0.31
MutPred		0.15		Loss of glycosylation at P182 (P = 0.0272);.;
MVP		0.043
MPC		0.20
ClinPred		0.37	T
GERP RS		1.8
Varity_R		0.068
gMVP		0.15

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

LitVar

Other links and lift over

dbSNP: rs202194930; hg19: chr7-100085889;