17-81940458-T-C

Position:

• chr17-81940458-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145113.3(MYADML2):​c.*360A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 214,374 control chromosomes in the GnomAD database, including 30,613 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (21047 hom., cov: 33)
  • Exomes 𝑓: 0.54 (9566 hom.)
• Consequence: MYADML2 NM_001145113.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYADML2	NM_001145113.3	c.*360A>G		3_prime_UTR_variant	3/3	ENST00000409745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYADML2	ENST00000409745.2	c.*360A>G		3_prime_UTR_variant	3/3	1	NM_001145113.3	P1
PYCR1	ENST00000579366.5	c.-24+292A>G		intron_variant		3
PYCR1	ENST00000582198.5	c.-24+1838A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77759 AN: 151996 Hom.: 21045 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.539 AC: 33584 AN: 62260 Hom.: 9566 Cov.: 0 AF XY: 0.537 AC XY: 17186 AN XY: 31990

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.481

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.511 AC: 77780 AN: 152114 Hom.: 21047 Cov.: 33 AF XY: 0.510 AC XY: 37914 AN XY: 74370

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.537

Alfa AF: 0.518 Hom.: 3343

Bravo AF: 0.491

Asia WGS AF: 0.419 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.67
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs2293099; hg19: chr17-79898334;