Variant 7-38391869-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001635.4(AMPH):c.1757C>T(p.Thr586Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,612,822 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 5 hom. )

Consequence

AMPH
NM_001635.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.623

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006348312).

BP6

Variant 7-38391869-G-A is Benign according to our data. Variant chr7-38391869-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 711336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPH	NM_001635.4 linkuse as main transcript	c.1757C>T	p.Thr586Met	missense_variant	19/21	ENST00000356264.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPH	ENST00000356264.7 linkuse as main transcript	c.1757C>T	p.Thr586Met	missense_variant	19/21	1	NM_001635.4	P3	P49418-1

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

271

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00269

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00198

AC:

495

AN:

249932

Hom.:

AF XY:

0.00200

AC XY:

270

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.00175

Gnomad ASJ exome

AF:

0.00301

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000884

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00294

AC:

4289

AN:

1460580

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

2077

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.000688

Gnomad4 AMR exome

AF:

0.00209

Gnomad4 ASJ exome

AF:

0.00364

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.000870

Gnomad4 FIN exome

AF:

0.000245

Gnomad4 NFE exome

AF:

0.00344

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00178

AC:

271

AN:

152242

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00269

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00272

Hom.:

Bravo

AF:

0.00182

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00187

AC:

227

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00379

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.031

Sift

Benign

0.13

T;T

Sift4G

Benign

0.095

T;D

Polyphen

0.0070

B;B

Vest4

0.077

MVP

0.66

MPC

0.20

ClinPred

0.0048

GERP RS

0.27

Varity_R

0.015

gMVP

0.21

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

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