rs774545284

Variant names:

• chr17-81941455-G-A
• rs774545284
• NM_001145113.3:c.287C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-81941455-G-A
• chr17-81941455-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001145113.3(MYADML2):​c.287C>T​(p.Thr96Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,397,094 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T96N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: MYADML2 NM_001145113.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.20

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

Our verdict: Uncertain_significance. The variant received 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.287C>T	p.Thr96Ile	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.287C>T	p.Thr96Ile	missense_variant	Exon 3 of 3	1	NM_001145113.3	ENSP00000386702.2
PYCR1	ENST00000582198.5	c.-24+841C>T		intron_variant	Intron 1 of 6	5		ENSP00000463226.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD2 exomes AF: 0.0000207 AC: 3 AN: 144774 AF XY: 0.0000128

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1397094 Hom.: 0 Cov.: 93 AF XY: 0.00000290 AC XY: 2 AN XY: 689046

African (AFR) AF: 0.00 AC: 0 AN: 31576

American (AMR) AF: 0.00 AC: 0 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35718

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078598

Other (OTH) AF: 0.0000345 AC: 2 AN: 57952

GnomAD4 genome Cov.: 35

ExAC AF: 0.0000237 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		9.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.29
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.86	P
Vest4		0.72
MutPred		0.64		Gain of helix (P = 0.0349);
MVP		0.10
ClinPred		0.87	D
GERP RS		4.9
PromoterAI		-0.00030	Neutral
Varity_R		0.44
gMVP		0.81
Mutation Taster		=31/69	disease causing

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: rs774545284; hg19: chr17-79899331;