rs749633074

Variant names:

• chr7-100486964-C-T
• rs749633074
• NM_173564.4:c.212C>T

Variant summary

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

The NM_173564.4(NYAP1):​c.212C>T​(p.Pro71Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,605,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: NYAP1 NM_173564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00
• 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 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.212C>T	p.Pro71Leu	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.212C>T	p.Pro71Leu	missense	Exon 3 of 7	ENSP00000300179.2	Q6ZVC0-1
	NYAP1	ENST00000880488.1		c.212C>T	p.Pro71Leu	missense	Exon 3 of 7	ENSP00000550547.1
	NYAP1	ENST00000880489.1		c.212C>T	p.Pro71Leu	missense	Exon 2 of 6	ENSP00000550548.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152054 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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000445 AC: 1 AN: 224796 AF XY: 0.00

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: 0.0000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1453920 Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8 AN XY: 722902

African (AFR) AF: 0.00 AC: 0 AN: 33344

American (AMR) AF: 0.0000228 AC: 1 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25902

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 85556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1109056

Other (OTH) AF: 0.00 AC: 0 AN: 59982

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152054 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74288

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000831 AC: 1

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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.82
MutPred		0.28		Gain of catalytic residue at P71 (P = 0.0073)
MVP		0.38
MPC		0.74
ClinPred		0.98	D
GERP RS		5.0
PromoterAI		0.0040	Neutral
Varity_R		0.37
gMVP		0.61
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749633074; hg19: chr7-100084587;