Genetic Variant NM_007224.4:c.843C>G (chr12-57225663-C-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007224.4(NXPH4):c.843C>G(p.Val281Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,613,944 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 3 hom. )

Consequence

NXPH4
NM_007224.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.22

Publications

0 publications found

Variant links:

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]

NXPH4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 12-57225663-C-G is Benign according to our data. Variant chr12-57225663-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2643131.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.22 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

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.843C>G	p.Val281Val	synonymous	Exon 2 of 2	NP_009155.1	O95158

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NXPH4	ENST00000349394.6	TSL:1 MANE Select	c.843C>G	p.Val281Val	synonymous	Exon 2 of 2	ENSP00000333593.6	O95158
NXPH4	ENST00000556415.1	TSL:2	n.*970C>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000452288.1	G3V5C5
NXPH4	ENST00000556415.1	TSL:2	n.*970C>G		3_prime_UTR	Exon 3 of 3	ENSP00000452288.1	G3V5C5

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00120

AC:

301

AN:

250728

AF XY:

0.00123

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000604

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000894

AC:

1306

AN:

1461632

Hom.:

Cov.:

AF XY:

0.000894

AC XY:

650

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000850

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00402

AC:

105

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000395

AC:

AN:

53182

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000955

AC:

1062

AN:

1112002

Other (OTH)

AF:

0.00108

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

166

250

333

416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000808

AC:

123

AN:

152312

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41572

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00131

AC:

AN:

68016

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.000895

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.5

(source)

DANN

Benign

0.58

PhyloP100

3.2

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over