Genetic Variant NM_001163922.3:c.1754A>G (chr19-51338184-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001163922.3(VSIG10L):c.1754A>G(p.His585Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000006 in 1,499,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H585Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

VSIG10L
NM_001163922.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.211

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02922079).

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.1754A>G	p.His585Arg	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.1754A>G	p.His585Arg	missense	Exon 6 of 10	ENSP00000335623.3	Q86VR7-1
VSIG10L	ENST00000600663.1	TSL:1	n.372A>G		non_coding_transcript_exon	Exon 3 of 7
VSIG10L	ENST00000915571.1		c.1754A>G	p.His585Arg	missense	Exon 6 of 11	ENSP00000585630.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151990

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:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000277

AC:

AN:

108320

AF XY:

0.0000531

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000322

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000445

AC:

AN:

1347400

Hom.:

Cov.:

AF XY:

0.00000909

AC XY:

AN XY:

659802

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29814

American (AMR)

AF:

0.00

AC:

AN:

27830

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21440

East Asian (EAS)

AF:

0.000170

AC:

AN:

35256

South Asian (SAS)

AF:

0.00

AC:

AN:

72092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5380

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1053190

Other (OTH)

AF:

0.00

AC:

AN:

55668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41376

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.0000302

ExAC

AF:

0.0000377

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.9

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0096

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.45

M_CAP

Benign

0.0097

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

PhyloP100

-0.21

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.1

REVEL

Benign

0.028

Sift

Benign

0.45

Sift4G

Benign

0.51

Polyphen

0.0020

Vest4

0.10

MutPred

0.39

Loss of catalytic residue at L587 (P = 0.0429)

MVP

0.014

ClinPred

0.019

GERP RS

0.20

Varity_R

0.068

gMVP

0.25

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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