Variant chr17-81940913-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145113.3(MYADML2):c.829C>A(p.Gln277Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000579 in 1,547,398 control chromosomes in the GnomAD database, including 3 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 3 hom. )

Consequence

MYADML2
NM_001145113.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.09

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060272276).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYADML2	NM_001145113.3 linkuse as main transcript	c.829C>A	p.Gln277Lys	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.829C>A	p.Gln277Lys	missense_variant	3/3	1	NM_001145113.3	P1
PYCR1	ENST00000579366.5 linkuse as main transcript	c.-187C>A		5_prime_UTR_variant	1/4	3
PYCR1	ENST00000582198.5 linkuse as main transcript	c.-24+1383C>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000297

AC:

AN:

154718

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

82186

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000537

Gnomad OTH exome

AF:

0.00138

GnomAD4 exome

AF:

0.000605

AC:

844

AN:

1395274

Hom.:

Cov.:

AF XY:

0.000585

AC XY:

402

AN XY:

687426

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.000309

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.0000416

Gnomad4 NFE exome

AF:

0.000708

Gnomad4 OTH exome

AF:

0.000484

GnomAD4 genome

AF:

0.000342

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000328

Hom.:

Bravo

AF:

0.000363

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ExAC

AF:

0.000277

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

Oct 12, 2021

The c.829C>A (p.Q277K) 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 829, causing the glutamine (Q) at amino acid position 277 to be replaced by a lysine (K). 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

0.16

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.16

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

M_CAP

Benign

0.0077

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.29

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.38

REVEL

Benign

0.060

Sift

Benign

0.44

Sift4G

Benign

0.83

Polyphen

0.061

Vest4

0.16

MVP

0.040

ClinPred

0.030

GERP RS

4.7

Varity_R

0.25

gMVP

0.69

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