chr17-81941056-C-A

Variant names:

• chr17-81941056-C-A
• NM_001145113.3:c.686G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145113.3(MYADML2):​c.686G>T​(p.Arg229Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MYADML2 NM_001145113.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYADML2	NM_001145113.3	c.686G>T	p.Arg229Leu	missense_variant	Exon 3 of 3	ENST00000409745.2	NP_001138585.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYADML2	ENST00000409745.2	c.686G>T	p.Arg229Leu	missense_variant	Exon 3 of 3	1	NM_001145113.3	ENSP00000386702.2
PYCR1	ENST00000579366.5	c.-330G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	3		ENSP00000462398.1
PYCR1	ENST00000579366.5	c.-330G>T		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000462398.1
PYCR1	ENST00000582198.5	c.-24+1240G>T		intron_variant	Intron 1 of 6	5		ENSP00000463226.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.686G>T (p.R229L) alteration is located in exon 3 (coding exon 1) of the MYADML2 gene. This alteration results from a G to T substitution at nucleotide position 686, causing the arginine (R) at amino acid position 229 to be replaced by a leucine (L). 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	0.32
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0082	T
Eigen	Benign	0.053
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.20
Sift	Benign	0.46	T
Sift4G	Benign	0.49	T
Polyphen		0.72	P
Vest4		0.71
MutPred		0.44		Loss of solvent accessibility (P = 0.1144);
MVP		0.11
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.24
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79898932;