chr12-57224954-C-T

Variant names:

• chr12-57224954-C-T
• rs1340574300
• NM_007224.4:c.134C>T

Variant summary

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

The NM_007224.4(NXPH4):​c.134C>T​(p.Ala45Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000239 in 1,253,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: NXPH4 NM_007224.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0680
• Publications: 1 publications found

Genes affected

NXPH4 (HGNC:8078): (neurexophilin 4) Predicted to enable signaling receptor binding activity. Predicted to be located in extracellular region. [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=0.071033865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007224.4. 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
	NXPH4	NM_007224.4	MANE Select	c.134C>T	p.Ala45Val	missense	Exon 2 of 2	NP_009155.1	O95158

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPH4	ENST00000349394.6	TSL:1 MANE Select	c.134C>T	p.Ala45Val	missense	Exon 2 of 2	ENSP00000333593.6	O95158
	NXPH4	ENST00000555154.1	TSL:3	n.185C>T		non_coding_transcript_exon	Exon 2 of 2
	NXPH4	ENST00000556415.1	TSL:2	n.*261C>T		non_coding_transcript_exon	Exon 3 of 3	ENSP00000452288.1	G3V5C5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000239 AC: 3 AN: 1253002 Hom.: 0 Cov.: 28 AF XY: 0.00000327 AC XY: 2 AN XY: 612108

African (AFR) AF: 0.00 AC: 0 AN: 25088

American (AMR) AF: 0.00 AC: 0 AN: 19182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18804

East Asian (EAS) AF: 0.00 AC: 0 AN: 29822

South Asian (SAS) AF: 0.00 AC: 0 AN: 58750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4450

European-Non Finnish (NFE) AF: 9.91e-7 AC: 1 AN: 1008672

Other (OTH) AF: 0.0000389 AC: 2 AN: 51470

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.080
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.068
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.079
Sift	Uncertain	0.017	D
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.40		Gain of catalytic residue at G42 (P = 0.001)
MVP		0.067
MPC		0.87
ClinPred		0.080	T
GERP RS		2.8
Varity_R		0.054
gMVP		0.31
Mutation Taster		=96/4	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: rs1340574300; hg19: chr12-57618737;