rs11578336

Positions:

• chr1-166989473-T-A
• chr1-166989473-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032858.3(MAEL):​c.121T>A​(p.Ser41Thr) 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. 14/21 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. S41A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAEL NM_032858.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07029942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAEL	NM_032858.3	c.121T>A	p.Ser41Thr	missense_variant	1/12	ENST00000367872.9	NP_116247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAEL	ENST00000367872.9	c.121T>A	p.Ser41Thr	missense_variant	1/12	1	NM_032858.3	ENSP00000356846.4
MAEL	ENST00000367870.6	c.121T>A	p.Ser41Thr	missense_variant	1/11	1		ENSP00000356844.2
MAEL	ENST00000622874	c.-48T>A		5_prime_UTR_variant	2/13	1		ENSP00000482771.1
MAEL	ENST00000447624.1	c.121T>A	p.Ser41Thr	missense_variant	1/9	3		ENSP00000402143.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000499 AC: 1 AN: 200332 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 107154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000663

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1432326 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 709316

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.3
DANN	Benign	0.43
DEOGEN2	Benign	0.022	.;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.079	T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.68	N;N;N
REVEL	Benign	0.041
Sift	Benign	0.45	T;T;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.17
MutPred		0.58		Loss of disorder (P = 0.0721);Loss of disorder (P = 0.0721);Loss of disorder (P = 0.0721);
MVP		0.24
MPC		0.17
ClinPred		0.020	T
GERP RS		2.5
Varity_R		0.034
gMVP		0.17

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: rs11578336; hg19: chr1-166958710;