19-41956914-C-G

Variant names:

• chr19-41956914-C-G
• rs781849637
• NM_006423.3:c.490G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006423.3(RABAC1):​c.490G>C​(p.Gly164Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G164S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RABAC1 NM_006423.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.30
• Publications: 0 publications found

Genes affected

RABAC1 (HGNC:9794): (Rab acceptor 1) Enables identical protein binding activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285505 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.895

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006423.3. 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
	RABAC1	NM_006423.3	MANE Select	c.490G>C	p.Gly164Arg	missense	Exon 5 of 5	NP_006414.2	Q9UI14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABAC1	ENST00000222008.11	TSL:1 MANE Select	c.490G>C	p.Gly164Arg	missense	Exon 5 of 5	ENSP00000222008.5	Q9UI14
	ENSG00000285505	ENST00000644613.1		n.*312G>C		non_coding_transcript_exon	Exon 25 of 25	ENSP00000494711.1	A0A2R8YEY8
	ENSG00000285505	ENST00000644613.1		n.*312G>C		3_prime_UTR	Exon 25 of 25	ENSP00000494711.1	A0A2R8YEY8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.31
Sift	Benign	0.088	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.80
MutPred		0.81		Gain of methylation at G164 (P = 0.0229)
MVP		0.72
MPC		1.6
ClinPred		0.95	D
GERP RS		3.6
Varity_R		0.22
gMVP		0.93
Mutation Taster		=20/80	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs781849637; hg19: chr19-42461066;