NM_002907.4:c.*192T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002907.4(RECQL):​c.*192T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000929 in 711,578 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00088 ( 3 hom. )

Consequence

RECQL
NM_002907.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.786
Variant links:
Genes affected
RECQL (HGNC:9948): (RecQ like helicase) The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer. [provided by RefSeq, Jan 2017]
PYROXD1 (HGNC:26162): (pyridine nucleotide-disulphide oxidoreductase domain 1) This gene encodes a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins that catalyze the pyridine nucleotide-dependent reduction of thiol residues in other proteins. The encoded protein belongs to the class I pyridine nucleotide-disulphide oxidoreductase family but lacks the C-terminal dimerization domain found in other family members and instead has a C-terminal nitrile reductase domain. It localizes to the nucleus and to striated sarcomeric compartments. Naturally occurring mutations in this gene cause early-onset myopathy with internalized nuclei and myofibrillar disorganization. A pseudogene of this gene has been defined on chromosome 11. [provided by RefSeq, Apr 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 12-21470002-A-G is Benign according to our data. Variant chr12-21470002-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1201812.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00112 (171/152194) while in subpopulation EAS AF= 0.000385 (2/5192). AF 95% confidence interval is 0.000267. There are 1 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RECQLNM_002907.4 linkc.*192T>C 3_prime_UTR_variant Exon 15 of 15 ENST00000444129.7 NP_002898.2
PYROXD1NM_024854.5 linkc.*1248A>G 3_prime_UTR_variant Exon 12 of 12 ENST00000240651.14 NP_079130.2 Q8WU10-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RECQLENST00000444129 linkc.*192T>C 3_prime_UTR_variant Exon 15 of 15 2 NM_002907.4 ENSP00000416739.2 P46063
PYROXD1ENST00000240651.14 linkc.*1248A>G 3_prime_UTR_variant Exon 12 of 12 1 NM_024854.5 ENSP00000240651.9 Q8WU10-1
RECQLENST00000421138 linkc.*192T>C 3_prime_UTR_variant Exon 16 of 16 1 ENSP00000395449.2 P46063
PYROXD1ENST00000538582.5 linkc.*1248A>G 3_prime_UTR_variant Exon 12 of 12 2 ENSP00000438505.1 Q8WU10-2

Frequencies

GnomAD3 genomes
AF:
0.00112
AC:
171
AN:
152078
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0131
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000382
Gnomad OTH
AF:
0.000957
GnomAD4 exome
AF:
0.000876
AC:
490
AN:
559384
Hom.:
3
Cov.:
8
AF XY:
0.000827
AC XY:
233
AN XY:
281664
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000258
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0131
Gnomad4 NFE exome
AF:
0.000158
Gnomad4 OTH exome
AF:
0.000859
GnomAD4 genome
AF:
0.00112
AC:
171
AN:
152194
Hom.:
1
Cov.:
32
AF XY:
0.00152
AC XY:
113
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0131
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.00106
Hom.:
0
Bravo
AF:
0.000128

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Nov 23, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
8.8
DANN
Benign
0.85

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.

Other links and lift over

dbSNP: rs189275364; hg19: chr12-21622936; API