Variant 2-127873991-C-G 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_001199140.2(AMMECR1L):c.244G>C(p.Ala82Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,202 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 142 hom. )

Consequence

AMMECR1L
NM_001199140.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.935

Variant links:

Genes affected

AMMECR1L (HGNC:28658): (AMMECR1 like) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

AMMECR1L links:

LOC107985803 (HGNC:):

LOC107985803 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=0.0047555566).

BP6

Variant 2-127873991-C-G is Benign according to our data. Variant chr2-127873991-C-G is described in ClinVar as [Benign]. Clinvar id is 769573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1291 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMMECR1L	NM_001199140.2 link	c.244G>C	p.Ala82Pro	missense_variant	3/8	ENST00000272647.10	NP_001186069.1	Q6DCA0A0A024RAG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMMECR1L	ENST00000272647.10 link	c.244G>C	p.Ala82Pro	missense_variant	3/8	1	NM_001199140.2	ENSP00000272647.6		Q6DCA0

Frequencies

GnomAD3 genomes

AF:

0.00849

AC:

1292

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00811

AC:

2039

AN:

251476

Hom.:

AF XY:

0.00817

AC XY:

1111

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00546

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00559

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00945

GnomAD4 exome

AF:

0.0119

AC:

17448

AN:

1461890

Hom.:

142

Cov.:

AF XY:

0.0118

AC XY:

8568

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00517

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00594

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.00848

AC:

1291

AN:

152312

Hom.:

Cov.:

AF XY:

0.00846

AC XY:

630

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00970

Hom.:

Bravo

AF:

0.00822

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0135

AC:

116

ExAC

AF:

0.00788

AC:

957

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0120

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

.;D

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.027

Sift

Benign

0.12

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0

B;B

Vest4

0.17

MVP

0.11

MPC

0.45

ClinPred

0.023

GERP RS

3.3

Varity_R

0.067

gMVP

0.73

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