rs755136215

Variant names:

• chr1-166989410-C-A
• rs755136215
• NM_032858.3:c.58C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-166989410-C-A
• chr1-166989410-C-G

Variant summary

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

The NM_032858.3(MAEL):​c.58C>A​(p.Pro20Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,453,976 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. P20A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAEL NM_032858.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.10
• Publications: 0 publications found

Genes affected

MAEL (HGNC:25929): (maelstrom spermatogenic transposon silencer) Predicted to enable sequence-specific DNA binding activity. Predicted to be involved in gamete generation; negative regulation of macromolecule metabolic process; and piRNA metabolic process. Predicted to act upstream of or within several processes, including homologous chromosome pairing at meiosis; intrinsic apoptotic signaling pathway in response to DNA damage; and negative regulation of macromolecule metabolic process. Predicted to be located in piP-body. Predicted to be active in P granule and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032858.3. 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
	MAEL	NM_032858.3	MANE Select	c.58C>A	p.Pro20Thr	missense	Exon 1 of 12	NP_116247.1	A0A140VJP0
	MAEL	NM_001286377.2		c.58C>A	p.Pro20Thr	missense	Exon 1 of 11	NP_001273306.1	Q96JY0-2
	MAEL	NM_001286378.2		c.-111C>A		5_prime_UTR	Exon 2 of 13	NP_001273307.1	E9JVC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEL	ENST00000367872.9	TSL:1 MANE Select	c.58C>A	p.Pro20Thr	missense	Exon 1 of 12	ENSP00000356846.4	Q96JY0-1
	MAEL	ENST00000367870.6	TSL:1	c.58C>A	p.Pro20Thr	missense	Exon 1 of 11	ENSP00000356844.2	Q96JY0-2
	MAEL	ENST00000622874.4	TSL:1	c.-111C>A		5_prime_UTR	Exon 2 of 13	ENSP00000482771.1	E9JVC4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453976 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722268

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 43520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.00 AC: 0 AN: 84500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108686

Other (OTH) AF: 0.00 AC: 0 AN: 60132

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.71		Gain of helix (P = 0.0349)
MVP		0.69
MPC		0.78
ClinPred		0.99	D
GERP RS		5.5
PromoterAI		0.042	Neutral
Varity_R		0.56
gMVP		0.57
Mutation Taster		=55/45	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: rs755136215; hg19: chr1-166958647;