Genetic Variant RAB44:p.Ser778Pro (chr6-36722466-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001257357.2(RAB44):c.2332T>C(p.Ser778Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,447,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

RAB44
NM_001257357.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.925

Publications

1 publications found

Variant links:

Genes affected

RAB44 (HGNC:21068): (RAB44, member RAS oncogene family) Predicted to enable GTP binding activity; GTPase activity; and calcium ion binding activity. Predicted to be located in azurophil granule membrane; plasma membrane; and specific granule membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB44 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047772527).

BP6

Variant 6-36722466-T-C is Benign according to our data. Variant chr6-36722466-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2673060.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257357.2. 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
	RAB44	NM_001257357.2	MANE Select	c.2332T>C	p.Ser778Pro	missense	Exon 9 of 14	NP_001244286.1	Q7Z6P3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB44	ENST00000612677.6	TSL:5 MANE Select	c.2332T>C	p.Ser778Pro	missense	Exon 9 of 14	ENSP00000481054.1	Q7Z6P3
	RAB44	ENST00000957683.1		c.982T>C	p.Ser328Pro	missense	Exon 8 of 13	ENSP00000627742.1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

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:

0.00143

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00111

AC:

AN:

69444

AF XY:

0.00134

show subpopulations

Gnomad AFR exome

AF:

0.000352

Gnomad AMR exome

AF:

0.00248

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.00124

AC:

1606

AN:

1295196

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

761

AN XY:

628812

show subpopulations

African (AFR)

AF:

0.000139

AC:

AN:

28736

American (AMR)

AF:

0.00219

AC:

AN:

22794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19242

East Asian (EAS)

AF:

0.00

AC:

AN:

34710

South Asian (SAS)

AF:

0.00

AC:

AN:

62596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33494

Middle Eastern (MID)

AF:

0.000190

AC:

AN:

5256

European-Non Finnish (NFE)

AF:

0.00144

AC:

1492

AN:

1034398

Other (OTH)

AF:

0.00109

AC:

AN:

53970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

180

240

300

<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:

0.00106

AC:

161

AN:

152158

Hom.:

Cov.:

AF XY:

0.000941

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41498

American (AMR)

AF:

0.00366

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00143

AC:

AN:

67990

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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:

0.000776

Hom.:

Bravo

AF:

0.00105

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ExAC

AF:

0.000258

AC:

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

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.081

(source)

DANN

Benign

0.59

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0048

PhyloP100

-0.93

PrimateAI

Benign

0.31

Sift4G

Benign

0.35

Vest4

0.022

MVP

0.15

GERP RS

-1.7

Varity_R

0.052

gMVP

0.17

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