rs10213360

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is . The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080476.3(GRXCR1):c.627+8A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,611,240 control chromosomes in the GnomAD database, including 514,029 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 53345 hom., cov: 32)

Exomes 𝑓: 0.79 ( 460684 hom. )

Consequence

GRXCR1
NM_001080476.3 splice_region, intron

Scores

Splicing: ADA: 0.00002498

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.679

Publications

12 publications found

Variant links:

Genes affected

GRXCR1 (HGNC:31673): (glutaredoxin and cysteine rich domain containing 1) This gene is one of 60 loci associated with autosomal-recessive nonsyndromic hearing impairment. This gene encodes a protein which contains GRX-like domains; these domains play a role in the S-glutathionylation of proteins and may be involved in actin organization in hair cells. [provided by RefSeq, Sep 2010]

GRXCR1 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 25
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GRXCR1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001080476.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 4-42963142-A-C is Benign according to our data. Variant chr4-42963142-A-C is described in ClinVar as Benign. ClinVar VariationId is 43888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080476.3. 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
	GRXCR1	NM_001080476.3	MANE Select	c.627+8A>C		splice_region intron	N/A	NP_001073945.1	A8MXD5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRXCR1	ENST00000399770.3	TSL:1 MANE Select	c.627+8A>C		splice_region intron	N/A	ENSP00000382670.2	A8MXD5

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

126743

AN:

151738

Hom.:

53279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.914

Gnomad AMI

AF:

0.895

Gnomad AMR

AF:

0.856

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.986

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.834

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.786

Gnomad OTH

AF:

0.823

GnomAD2 exomes

AF:

0.813

AC:

202327

AN:

248980

AF XY:

0.799

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.898

Gnomad ASJ exome

AF:

0.717

Gnomad EAS exome

AF:

0.992

Gnomad FIN exome

AF:

0.829

Gnomad NFE exome

AF:

0.780

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

AF:

0.793

AC:

1156803

AN:

1459384

Hom.:

460684

Cov.:

AF XY:

0.788

AC XY:

572107

AN XY:

726088

show subpopulations

African (AFR)

AF:

0.920

AC:

30706

AN:

33386

American (AMR)

AF:

0.893

AC:

39899

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

18722

AN:

26060

East Asian (EAS)

AF:

0.991

AC:

39317

AN:

39690

South Asian (SAS)

AF:

0.699

AC:

60255

AN:

86206

European-Finnish (FIN)

AF:

0.827

AC:

44160

AN:

53416

Middle Eastern (MID)

AF:

0.724

AC:

4162

AN:

5752

European-Non Finnish (NFE)

AF:

0.785

AC:

871722

AN:

1109928

Other (OTH)

AF:

0.794

AC:

47860

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

11838

23676

35513

47351

59189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20656

41312

61968

82624

103280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.835

AC:

126870

AN:

151856

Hom.:

53345

Cov.:

AF XY:

0.837

AC XY:

62133

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.914

AC:

37931

AN:

41488

American (AMR)

AF:

0.856

AC:

13016

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

2449

AN:

3464

East Asian (EAS)

AF:

0.986

AC:

5078

AN:

5148

South Asian (SAS)

AF:

0.715

AC:

3436

AN:

4808

European-Finnish (FIN)

AF:

0.834

AC:

8844

AN:

10604

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.786

AC:

53347

AN:

67836

Other (OTH)

AF:

0.824

AC:

1727

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1040

2081

3121

4162

5202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.786

Hom.:

38766

Bravo

AF:

0.844

Asia WGS

AF:

0.852

AC:

2958

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Autosomal recessive nonsyndromic hearing loss 25 (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.43

(source)

DANN

Benign

0.62

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0020

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over