rs7518979

Variant names:

• chr1-205843784-A-C
• rs7518979
• NM_152491.5:c.710T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-205843784-A-C
• chr1-205843784-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152491.5(PM20D1):​c.710T>G​(p.Ile237Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. I237T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PM20D1 NM_152491.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.96
• Publications: 20 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PM20D1	NM_152491.5	MANE Select	c.710T>G	p.Ile237Ser	missense splice_region	Exon 6 of 13	NP_689704.4
	PM20D1	NR_135186.2		n.770T>G		splice_region non_coding_transcript_exon	Exon 6 of 12

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PM20D1	ENST00000367136.5	TSL:1 MANE Select	c.710T>G	p.Ile237Ser	missense splice_region	Exon 6 of 13	ENSP00000356104.4
	PM20D1	ENST00000460624.5	TSL:2	n.770T>G		splice_region non_coding_transcript_exon	Exon 6 of 12
	PM20D1-AS1	ENST00000653632.1		n.234-10004A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		8.0
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.62		Gain of disorder (P = 0.0041)
MVP		0.48
MPC		0.58
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.95
gMVP		0.99
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7518979; hg19: chr1-205812912;