rs1138675

Variant names:

• chr12-21469761-A-G
• rs1138675
• NM_002907.4:c.*433T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-21469761-A-G
• chr12-21469761-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002907.4(RECQL):​c.*433T>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 0.183 in 153,596 control chromosomes in the GnomAD database, including 2,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2586 hom., cov: 31)
  • Exomes 𝑓: 0.17 (45 hom.)
• Consequence: RECQL NM_002907.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.726
• Publications: 3 publications found

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]

PYROXD1 Gene-Disease associations (from GenCC):

• myofibrillar myopathy 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-21469761-A-G is Benign according to our data. Variant chr12-21469761-A-G is described in ClinVar as Benign. ClinVar VariationId is 1292479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002907.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	NM_002907.4	MANE Select	c.*433T>C		3_prime_UTR	Exon 15 of 15	NP_002898.2
	PYROXD1	NM_024854.5	MANE Select	c.*1007A>G		3_prime_UTR	Exon 12 of 12	NP_079130.2	Q8WU10-1
	RECQL	NM_032941.3		c.*433T>C		3_prime_UTR	Exon 16 of 16	NP_116559.1	P46063

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	ENST00000444129.7	TSL:2 MANE Select	c.*433T>C		3_prime_UTR	Exon 15 of 15	ENSP00000416739.2	P46063
	PYROXD1	ENST00000240651.14	TSL:1 MANE Select	c.*1007A>G		3_prime_UTR	Exon 12 of 12	ENSP00000240651.9	Q8WU10-1
	RECQL	ENST00000965023.1		c.*433T>C		3_prime_UTR	Exon 16 of 16	ENSP00000635082.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27629 AN: 150740 Hom.: 2582 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0678

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.167 AC: 457 AN: 2734 Hom.: 45 Cov.: 0 AF XY: 0.169 AC XY: 274 AN XY: 1626

African (AFR) AF: 0.143 AC: 2 AN: 14

American (AMR) AF: 0.122 AC: 30 AN: 246

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 3 AN: 14

East Asian (EAS) AF: 0.0806 AC: 5 AN: 62

South Asian (SAS) AF: 0.113 AC: 24 AN: 212

European-Finnish (FIN) AF: 0.179 AC: 30 AN: 168

Middle Eastern (MID) AF: 0.167 AC: 1 AN: 6

European-Non Finnish (NFE) AF: 0.178 AC: 340 AN: 1908

Other (OTH) AF: 0.212 AC: 22 AN: 104

GnomAD4 genome AF: 0.183 AC: 27644 AN: 150862 Hom.: 2586 Cov.: 31 AF XY: 0.180 AC XY: 13298 AN XY: 73746

African (AFR) AF: 0.240 AC: 9828 AN: 41002

American (AMR) AF: 0.157 AC: 2379 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 648 AN: 3456

East Asian (EAS) AF: 0.0679 AC: 350 AN: 5154

South Asian (SAS) AF: 0.104 AC: 500 AN: 4790

European-Finnish (FIN) AF: 0.154 AC: 1604 AN: 10446

Middle Eastern (MID) AF: 0.280 AC: 80 AN: 286

European-Non Finnish (NFE) AF: 0.171 AC: 11590 AN: 67612

Other (OTH) AF: 0.190 AC: 398 AN: 2100

Alfa AF: 0.0563 Hom.: 63

Asia WGS AF: 0.125 AC: 437 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.37
PhyloP100		-0.73
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: rs1138675; hg19: chr12-21622695;