Genetic Variant C19orf81:p.Arg131Ser (chr19-50658118-C-A) – 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_001195076.2(C19orf81):c.391C>A(p.Arg131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000835 in 1,533,346 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 1 hom. )

Consequence

C19orf81
NM_001195076.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

Publications

0 publications found

Variant links:

Genes affected

C19orf81 (HGNC:40041): (chromosome 19 open reading frame 81)

C19orf81 links:

SYT3 (HGNC:11511): (synaptotagmin 3) Predicted to enable several functions, including phospholipid binding activity; protein dimerization activity; and syntaxin binding activity. Involved in positive regulation of dendrite extension. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

SYT3 links:

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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=0.042907894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195076.2. 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
	C19orf81	NM_001195076.2	MANE Select	c.391C>A	p.Arg131Ser	missense	Exon 4 of 5	NP_001182005.1	C9J6K1
	SYT3	NM_001424346.1		c.-262G>T		upstream_gene	N/A	NP_001411275.1	Q9BQG1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C19orf81	ENST00000425202.6	TSL:5 MANE Select	c.391C>A	p.Arg131Ser	missense	Exon 4 of 5	ENSP00000417035.1	C9J6K1
C19orf81	ENST00000850965.1		c.799C>A	p.Arg267Ser	missense	Exon 4 of 5	ENSP00000521049.1
C19orf81	ENST00000850964.1		c.391C>A	p.Arg131Ser	missense	Exon 5 of 6	ENSP00000521048.1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.000287

AC:

AN:

132224

AF XY:

0.000236

show subpopulations

Gnomad AFR exome

AF:

0.000156

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000291

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.0000681

AC:

AN:

1381216

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

681510

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31490

American (AMR)

AF:

0.00150

AC:

AN:

35242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25030

East Asian (EAS)

AF:

0.000814

AC:

AN:

35610

South Asian (SAS)

AF:

0.00

AC:

AN:

78958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5572

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1077728

Other (OTH)

AF:

0.000104

AC:

AN:

57766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000223

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41490

American (AMR)

AF:

0.00157

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68012

Other (OTH)

AF:

0.000476

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000712

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.0000679

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Pathogenic

0.76

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.72

M_CAP

Benign

0.041

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

1.9

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.11

Sift

Uncertain

0.015

Sift4G

Pathogenic

0.0

Vest4

0.37

MutPred

0.36

Loss of MoRF binding (P = 0.0226)

MVP

0.067

ClinPred

0.082

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.25

gMVP

0.18

Mutation Taster

=81/19

polymorphism

(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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over