Variant chr17-81940924-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001145113.3(MYADML2):c.818C>A(p.Pro273His) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,549,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

MYADML2
NM_001145113.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

Variant links:

Genes affected

MYADML2 (HGNC:34548): (myeloid associated differentiation marker like 2) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYADML2 links:

PYCR1 (HGNC:9721): (pyrroline-5-carboxylate reductase 1) This gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may also play a physiologic role in the generation of NADP(+) in some cell types. The protein forms a homopolymer and localizes to the mitochondrion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

PYCR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28303114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYADML2	NM_001145113.3 linkuse as main transcript	c.818C>A	p.Pro273His	missense_variant	3/3	ENST00000409745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MYADML2	ENST00000409745.2 linkuse as main transcript	c.818C>A	p.Pro273His	missense_variant	3/3	1	NM_001145113.3	P1
PYCR1	ENST00000579366.5 linkuse as main transcript	c.-198C>A		5_prime_UTR_variant	1/4	3
PYCR1	ENST00000582198.5 linkuse as main transcript	c.-24+1372C>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000103

AC:

AN:

155146

Hom.:

AF XY:

0.0000971

AC XY:

AN XY:

82418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.000688

GnomAD4 exome

AF:

0.000120

AC:

167

AN:

1396998

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

688712

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000336

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:

0.000128

Gnomad4 OTH exome

AF:

0.000259

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000752

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.0000796

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.818C>A (p.P273H) alteration is located in exon 3 (coding exon 1) of the MYADML2 gene. This alteration results from a C to A substitution at nucleotide position 818, causing the proline (P) at amino acid position 273 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

M_CAP

Benign

0.0099

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.72

N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.063

Sift

Benign

0.18

Sift4G

Benign

0.59

Polyphen

0.93

Vest4

0.42

MVP

0.14

ClinPred

0.16

GERP RS

3.7

Varity_R

0.16

gMVP

0.62

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