1-205832637-C-G

Variant names:

• chr1-205832637-C-G
• rs142134039
• NM_152491.5:c.1246G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152491.5(PM20D1):​c.1246G>C​(p.Val416Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. V416I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PM20D1 NM_152491.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 0 publications found

Genes affected

PM20D1 (HGNC:26518): (peptidase M20 domain containing 1) Enables hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides. Involved in several processes, including amide biosynthetic process; cellular amide catabolic process; and negative regulation of neuron death. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

PM20D1-AS1 (HGNC:27633): (PM20D1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10800117).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152491.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PM20D1	NM_152491.5	MANE Select	c.1246G>C	p.Val416Leu	missense	Exon 11 of 13	NP_689704.4
	PM20D1	NR_135186.2		n.1244G>C		non_coding_transcript_exon	Exon 10 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PM20D1	ENST00000367136.5	TSL:1 MANE Select	c.1246G>C	p.Val416Leu	missense	Exon 11 of 13	ENSP00000356104.4	Q6GTS8-1
	PM20D1	ENST00000460624.5	TSL:2	n.1244G>C		non_coding_transcript_exon	Exon 10 of 12
	PM20D1	ENST00000461807.1	TSL:3	n.142-2258G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.87	L
PhyloP100		0.053
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.019
Sift	Benign	0.069	T
Sift4G	Benign	0.12	T
Polyphen		0.039	B
Vest4		0.14
MutPred		0.58		Loss of helix (P = 0.3949)
MVP		0.088
MPC		0.098
ClinPred		0.46	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.72
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142134039; hg19: chr1-205801765;