Genetic Variant VSIG10L:p.Arg627His (chr19-51338058-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001163922.3(VSIG10L):c.1880G>A(p.Arg627His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,551,558 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 201 hom., cov: 31)

Exomes 𝑓: 0.0026 ( 173 hom. )

Consequence

VSIG10L
NM_001163922.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.81

Publications

5 publications found

Variant links:

Genes affected

VSIG10L (HGNC:27111): (V-set and immunoglobulin domain containing 10 like) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

VSIG10L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.002365768).

BP6

Variant 19-51338058-C-T is Benign according to our data. Variant chr19-51338058-C-T is described in ClinVar as Benign. ClinVar VariationId is 769044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163922.3. 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
	VSIG10L	NM_001163922.3	MANE Select	c.1880G>A	p.Arg627His	missense	Exon 6 of 10	NP_001157394.1	Q86VR7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VSIG10L	ENST00000335624.5	TSL:5 MANE Select	c.1880G>A	p.Arg627His	missense	Exon 6 of 10	ENSP00000335623.3	Q86VR7-1
VSIG10L	ENST00000600663.1	TSL:1	n.498G>A		non_coding_transcript_exon	Exon 3 of 7
VSIG10L	ENST00000915571.1		c.1880G>A	p.Arg627His	missense	Exon 6 of 11	ENSP00000585630.1

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4043

AN:

152092

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0937

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0187

GnomAD2 exomes

AF:

0.00555

AC:

868

AN:

156452

AF XY:

0.00421

show subpopulations

Gnomad AFR exome

AF:

0.0949

Gnomad AMR exome

AF:

0.00377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000661

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.00262

AC:

3671

AN:

1399350

Hom.:

173

Cov.:

AF XY:

0.00229

AC XY:

1580

AN XY:

690184

show subpopulations

African (AFR)

AF:

0.0982

AC:

3102

AN:

31598

American (AMR)

AF:

0.00479

AC:

171

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25174

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.000202

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49260

Middle Eastern (MID)

AF:

0.00211

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000584

AC:

AN:

1078956

Other (OTH)

AF:

0.00529

AC:

307

AN:

58000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

212

424

636

848

1060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.0267

AC:

4058

AN:

152208

Hom.:

201

Cov.:

AF XY:

0.0257

AC XY:

1913

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0938

AC:

3894

AN:

41502

American (AMR)

AF:

0.00673

AC:

103

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00104

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68006

Other (OTH)

AF:

0.0185

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

178

356

534

712

890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.00603

Hom.:

Bravo

AF:

0.0302

ESP6500AA

AF:

0.0954

AC:

132

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.0104

AC:

276

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.014

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.8

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

REVEL

Benign

0.070

Sift

Benign

0.049

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.11

ClinPred

0.026

GERP RS

4.0

Varity_R

0.062

gMVP

0.39

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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