1-166989364-T-C

Variant names:

• chr1-166989364-T-C
• rs2296837
• NM_032858.3:c.12T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032858.3(MAEL):​c.12T>C​(p.Arg4Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,608,538 control chromosomes in the GnomAD database, including 54,234 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8513 hom., cov: 33)
  • Exomes 𝑓: 0.25 (45721 hom.)
• Consequence: MAEL NM_032858.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 11 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.039 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAEL	NM_032858.3	c.12T>C	p.Arg4Arg	synonymous_variant	Exon 1 of 12	ENST00000367872.9	NP_116247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAEL	ENST00000367872.9	c.12T>C	p.Arg4Arg	synonymous_variant	Exon 1 of 12	1	NM_032858.3	ENSP00000356846.4
MAEL	ENST00000367870.6	c.12T>C	p.Arg4Arg	synonymous_variant	Exon 1 of 11	1		ENSP00000356844.2
MAEL	ENST00000622874.4	c.-120-37T>C		intron_variant	Intron 1 of 12	1		ENSP00000482771.1
MAEL	ENST00000447624.1	c.12T>C	p.Arg4Arg	synonymous_variant	Exon 1 of 9	3		ENSP00000402143.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46705 AN: 152108 Hom.: 8501 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.270

GnomAD2 exomes AF: 0.230 AC: 55267 AN: 240318 AF XY: 0.225

Gnomad AFR exome AF: 0.526

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.225

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.238

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.246 AC: 357542 AN: 1456312 Hom.: 45721 Cov.: 33 AF XY: 0.242 AC XY: 175125 AN XY: 723752

African (AFR) AF: 0.531 AC: 17724 AN: 33400

American (AMR) AF: 0.156 AC: 6862 AN: 43974

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4450 AN: 26008

East Asian (EAS) AF: 0.230 AC: 9064 AN: 39492

South Asian (SAS) AF: 0.192 AC: 16306 AN: 85074

European-Finnish (FIN) AF: 0.203 AC: 10711 AN: 52888

Middle Eastern (MID) AF: 0.157 AC: 902 AN: 5756

European-Non Finnish (NFE) AF: 0.249 AC: 276811 AN: 1109534

Other (OTH) AF: 0.244 AC: 14712 AN: 60186

GnomAD4 genome AF: 0.307 AC: 46751 AN: 152226 Hom.: 8513 Cov.: 33 AF XY: 0.300 AC XY: 22337 AN XY: 74464

African (AFR) AF: 0.522 AC: 21667 AN: 41518

American (AMR) AF: 0.194 AC: 2962 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1235 AN: 5178

South Asian (SAS) AF: 0.195 AC: 942 AN: 4828

European-Finnish (FIN) AF: 0.197 AC: 2091 AN: 10616

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16544 AN: 68000

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.267 Hom.: 5244

Bravo AF: 0.317

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		-0.039
PromoterAI		-0.061	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2296837; hg19: chr1-166958601; COSMIC: COSV63304022; COSMIC: COSV63304022;