7-100487072-A-T

Variant names:

• chr7-100487072-A-T
• rs764706081
• NM_173564.4:c.320A>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.320A>T​(p.Glu107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: NYAP1 NM_173564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03
• 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=0.17558035).

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.320A>T	p.Glu107Val	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.320A>T	p.Glu107Val	missense	Exon 3 of 7	ENSP00000300179.2	Q6ZVC0-1
	NYAP1	ENST00000880488.1		c.320A>T	p.Glu107Val	missense	Exon 3 of 7	ENSP00000550547.1
	NYAP1	ENST00000880489.1		c.320A>T	p.Glu107Val	missense	Exon 2 of 6	ENSP00000550548.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000131 AC: 3 AN: 228814 AF XY: 0.00000794

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000622

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: 0.000181

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1444924 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717726

African (AFR) AF: 0.00 AC: 0 AN: 32438

American (AMR) AF: 0.0000702 AC: 3 AN: 42760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.00 AC: 0 AN: 38920

South Asian (SAS) AF: 0.00 AC: 0 AN: 84686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103894

Other (OTH) AF: 0.0000336 AC: 2 AN: 59502

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

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	Benign	0.23
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.13	T
Polyphen		0.56	P
Vest4		0.47
MutPred		0.18		Gain of MoRF binding (P = 0.0106)
MVP		0.043
MPC		0.47
ClinPred		0.58	D
GERP RS		3.0
PromoterAI		-0.026	Neutral
Varity_R		0.18
gMVP		0.29
Mutation Taster		=84/16	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: rs764706081; hg19: chr7-100084695;