Genetic Variant GVQW3:c.465+129T>C (chr11-76382422-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001305225.4(GVQW3):c.594T>C(p.Leu198Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GVQW3
NM_001305225.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.529

Publications

0 publications found

Variant links:

Genes affected

GVQW3 (HGNC:51239): (GVQW motif containing 3)

GVQW3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 11-76382422-T-C is Benign according to our data. Variant chr11-76382422-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2642166.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.529 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305225.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GVQW3	NM_001347885.2	MANE Select	c.465+129T>C		intron	N/A	NP_001334814.1	A0A0U1RQW1
GVQW3	NM_001305225.4		c.594T>C	p.Leu198Leu	synonymous	Exon 1 of 1	NP_001292154.1	Q3ZCU0-2
GVQW3	NM_001282456.4		c.382+212T>C		intron	N/A	NP_001269385.1	Q3ZCU0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GVQW3	ENST00000529331.2	TSL:2 MANE Select	c.465+129T>C		intron	N/A	ENSP00000489195.1	A0A0U1RQW1
GVQW3	ENST00000321844.6	TSL:1	c.382+212T>C		intron	N/A	ENSP00000323821.4	Q3ZCU0-1
GVQW3	ENST00000663165.1		c.594T>C	p.Leu198Leu	synonymous	Exon 1 of 1	ENSP00000499610.1	Q3ZCU0-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

565744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

304844

African (AFR)

AF:

0.00

AC:

AN:

15802

American (AMR)

AF:

0.00

AC:

AN:

33210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19714

East Asian (EAS)

AF:

0.00

AC:

AN:

32120

South Asian (SAS)

AF:

0.00

AC:

AN:

61852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4062

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

334848

Other (OTH)

AF:

0.00

AC:

AN:

31080

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

-0.53

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over