Variant 7-38436278-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001635.4(AMPH):c.1128G>C(p.Met376Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,613,478 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.027 ( 184 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 156 hom. )

Consequence

AMPH
NM_001635.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

AMPH (HGNC:471): (amphiphysin) This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff-man syndrome who were also affected by breast cancer are positive for autoantibodies against this protein. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences have not been determined. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Nov 2010]

AMPH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001930207).

BP6

Variant 7-38436278-C-G is Benign according to our data. Variant chr7-38436278-C-G is described in ClinVar as [Benign]. Clinvar id is 776216.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPH	NM_001635.4 linkuse as main transcript	c.1128G>C	p.Met376Ile	missense_variant	12/21	ENST00000356264.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPH	ENST00000356264.7 linkuse as main transcript	c.1128G>C	p.Met376Ile	missense_variant	12/21	1	NM_001635.4	P3	P49418-1
AMPH	ENST00000325590.9 linkuse as main transcript	c.1128G>C	p.Met376Ile	missense_variant	12/20	1		A2	P49418-2
AMPH	ENST00000441628.5 linkuse as main transcript	c.381G>C	p.Met127Ile	missense_variant	3/12	1

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4176

AN:

152148

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0925

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.00714

AC:

1796

AN:

251394

Hom.:

AF XY:

0.00545

AC XY:

741

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0937

Gnomad AMR exome

AF:

0.00628

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00266

AC:

3890

AN:

1461212

Hom.:

156

Cov.:

AF XY:

0.00234

AC XY:

1703

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.0890

Gnomad4 AMR exome

AF:

0.00731

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00686

GnomAD4 genome

AF:

0.0275

AC:

4181

AN:

152266

Hom.:

184

Cov.:

AF XY:

0.0273

AC XY:

2033

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0924

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.0326

ESP6500AA

AF:

0.0826

AC:

364

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00841

AC:

1021

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.13

.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.67

N;N

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.12

Sift

Benign

0.41

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.010

B;B

Vest4

0.48

MutPred

0.092

Loss of disorder (P = 0.049);Loss of disorder (P = 0.049);

MVP

0.74

MPC

0.21

ClinPred

0.0064

GERP RS

5.5

Varity_R

0.22

gMVP

0.087

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over