rs1340574300

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-57224954-C-A
• chr12-57224954-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007224.4(NXPH4):​c.134C>A​(p.Ala45Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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. A45V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NXPH4 NM_007224.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08636311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPH4	NM_007224.4	c.134C>A	p.Ala45Asp	missense_variant	Exon 2 of 2	ENST00000349394.6	NP_009155.1
NXPH4	XM_017018747.2	c.134C>A	p.Ala45Asp	missense_variant	Exon 2 of 3		XP_016874236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXPH4	ENST00000349394.6	c.134C>A	p.Ala45Asp	missense_variant	Exon 2 of 2	1	NM_007224.4	ENSP00000333593.6
NXPH4	ENST00000555154.1	n.185C>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
NXPH4	ENST00000556415.1	n.*261C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2		ENSP00000452288.1
NXPH4	ENST00000556415.1	n.*261C>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000452288.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1253006 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 612110

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.034
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.093	T
Polyphen		0.013	B
Vest4		0.22
MutPred		0.43		Gain of catalytic residue at A43 (P = 0.0055);
MVP		0.12
MPC		1.3
ClinPred		0.080	T
GERP RS		2.8
Varity_R		0.11
gMVP		0.48

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: rs1340574300; hg19: chr12-57618737;