Genetic Variant NM_001195076.2:c.112C>T (chr19-50656094-C-T) – 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.112C>T(p.Arg38Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,536,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

C19orf81
NM_001195076.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.167

Publications

1 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:

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=0.010867685).

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.112C>T	p.Arg38Trp	missense	Exon 2 of 5	NP_001182005.1	C9J6K1
	SYT3	NM_001424346.1		c.-154+1916G>A		intron	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.112C>T	p.Arg38Trp	missense	Exon 2 of 5	ENSP00000417035.1	C9J6K1
C19orf81	ENST00000850965.1		c.520C>T	p.Arg174Trp	missense	Exon 2 of 5	ENSP00000521049.1
C19orf81	ENST00000850964.1		c.112C>T	p.Arg38Trp	missense	Exon 3 of 6	ENSP00000521048.1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000134

AC:

AN:

134776

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000952

Gnomad FIN exome

AF:

0.000182

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000152

AC:

210

AN:

1383824

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

115

AN XY:

682856

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

31594

American (AMR)

AF:

0.0000280

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.000148

AC:

AN:

33890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.000181

AC:

195

AN:

1078888

Other (OTH)

AF:

0.0000691

AC:

AN:

57906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.000164

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41556

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000136

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000106

AC:

Asia WGS

AF:

0.000289

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

Benign

0.081

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.035

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.73

M_CAP

Benign

0.014

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

-0.17

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.059

Sift

Benign

0.16

Sift4G

Benign

0.076

Vest4

0.12

MVP

0.17

ClinPred

0.048

GERP RS

0.55

Varity_R

0.098

gMVP

0.30

Mutation Taster

=96/4

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

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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