rs12294513

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017704.3(ANKRD49):​c.-91+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Consequence

ANKRD49
NM_017704.3 splice_region, intron

Scores

2
Splicing: ADA: 0.0002204
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26
Variant links:
Genes affected
ANKRD49 (HGNC:25970): (ankyrin repeat domain 49) Involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
MRE11 (HGNC:7230): (MRE11 homolog, double strand break repair nuclease) This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD49NM_017704.3 linkc.-91+7T>A splice_region_variant, intron_variant Intron 1 of 2 ENST00000544612.6 NP_060174.2 Q8WVL7A0A024R398
MRE11NM_005591.4 linkc.-357A>T upstream_gene_variant ENST00000323929.8 NP_005582.1 P49959-1A0A024R395

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD49ENST00000544612.6 linkc.-91+7T>A splice_region_variant, intron_variant Intron 1 of 2 1 NM_017704.3 ENSP00000440396.1 Q8WVL7
MRE11ENST00000323929.8 linkc.-357A>T upstream_gene_variant 1 NM_005591.4 ENSP00000325863.4 P49959-1

Frequencies

GnomAD3 genomes
AF:
0.00112
AC:
170
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00377
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000955
GnomAD4 exome
Cov.:
0
GnomAD4 genome
AF:
0.00114
AC:
174
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.00125
AC XY:
93
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.00385
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000945
Bravo
AF:
0.00140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.34
DANN
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00022
dbscSNV1_RF
Benign
0.0
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs12294513; hg19: chr11-94227208; API