1-166980742-G-C

Variant names:

• chr1-166980742-G-C
• rs6682062
• ENST00000622874.4:c.-121+5076G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286378.2(MAEL):​c.-121+5076G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,984 control chromosomes in the GnomAD database, including 8,468 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 (8468 hom., cov: 31)
• Consequence: MAEL NM_001286378.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286378.2. 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
	MAEL	NM_001286378.2		c.-121+5076G>C		intron	N/A	NP_001273307.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEL	ENST00000622874.4	TSL:1	c.-121+5076G>C		intron	N/A	ENSP00000482771.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46597 AN: 151866 Hom.: 8462 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46637 AN: 151984 Hom.: 8468 Cov.: 31 AF XY: 0.300 AC XY: 22275 AN XY: 74312

African (AFR) AF: 0.522 AC: 21588 AN: 41392

American (AMR) AF: 0.194 AC: 2958 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3472

East Asian (EAS) AF: 0.237 AC: 1226 AN: 5170

South Asian (SAS) AF: 0.194 AC: 934 AN: 4814

European-Finnish (FIN) AF: 0.197 AC: 2086 AN: 10568

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

European-Non Finnish (NFE) AF: 0.243 AC: 16535 AN: 67968

Other (OTH) AF: 0.267 AC: 564 AN: 2112

Alfa AF: 0.121 Hom.: 185

Bravo AF: 0.317

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.70
PhyloP100		-0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6682062; hg19: chr1-166949979;