Variant chr1-166989364-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_032858.3(MAEL):c.12T>C(p.Arg4=) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390

Variant links:

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]

MAEL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MAEL	NM_032858.3 linkuse as main transcript	c.12T>C	p.Arg4=	synonymous_variant	1/12	ENST00000367872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAEL	ENST00000367872.9 linkuse as main transcript	c.12T>C	p.Arg4=	synonymous_variant	1/12	1	NM_032858.3	P1	Q96JY0-1
MAEL	ENST00000367870.6 linkuse as main transcript	c.12T>C	p.Arg4=	synonymous_variant	1/11	1			Q96JY0-2
MAEL	ENST00000622874.4 linkuse as main transcript	c.-120-37T>C		intron_variant		1
MAEL	ENST00000447624.1 linkuse as main transcript	c.12T>C	p.Arg4=	synonymous_variant	1/9	3

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46705

AN:

152108

Hom.:

8501

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.230

AC:

55267

AN:

240318

Hom.:

7144

AF XY:

0.225

AC XY:

29239

AN XY:

129930

show subpopulations

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 SAS exome

AF:

0.189

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.:

AF XY:

0.242

AC XY:

175125

AN XY:

723752

show subpopulations

Gnomad4 AFR exome

AF:

0.531

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.307

AC:

46751

AN:

152226

Hom.:

8513

Cov.:

AF XY:

0.300

AC XY:

22337

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.243

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.269

Hom.:

3383

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

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over