rs11578336

Variant names:

• chr1-166989473-T-A
• rs11578336
• NM_032858.3:c.121T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 24 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 0 ACMG points.

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

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.121T>A	p.Ser41Thr	missense	Exon 1 of 12	NP_116247.1
	MAEL	NM_001286377.2		c.121T>A	p.Ser41Thr	missense	Exon 1 of 11	NP_001273306.1
	MAEL	NM_001286378.2		c.-48T>A		5_prime_UTR	Exon 2 of 13	NP_001273307.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEL	ENST00000367872.9	TSL:1 MANE Select	c.121T>A	p.Ser41Thr	missense	Exon 1 of 12	ENSP00000356846.4
	MAEL	ENST00000367870.6	TSL:1	c.121T>A	p.Ser41Thr	missense	Exon 1 of 11	ENSP00000356844.2
	MAEL	ENST00000622874.4	TSL:1	c.-48T>A		5_prime_UTR	Exon 2 of 13	ENSP00000482771.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000499 AC: 1 AN: 200332 AF XY: 0.00

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33056

American (AMR) AF: 0.00 AC: 0 AN: 39626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25538

East Asian (EAS) AF: 0.00 AC: 0 AN: 38542

South Asian (SAS) AF: 0.00 AC: 0 AN: 82042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097286

Other (OTH) AF: 0.00 AC: 0 AN: 59388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.079	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.44
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.041
Sift	Benign	0.45	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.58		Loss of disorder (P = 0.0721)
MVP		0.24
MPC		0.17
ClinPred		0.020	T
GERP RS		2.5
PromoterAI		-0.038	Neutral
Varity_R		0.034
gMVP		0.17
Mutation Taster		=98/2	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: rs11578336; hg19: chr1-166958710;