rs781849637

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-41956914-C-A
• chr19-41956914-C-G
• chr19-41956914-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006423.3(RABAC1):​c.490G>T​(p.Gly164Cys) 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

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>T	p.Gly164Cys	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>T	p.Gly164Cys	missense	Exon 5 of 5	ENSP00000222008.5	Q9UI14
	ENSG00000285505	ENST00000644613.1		n.*312G>T		non_coding_transcript_exon	Exon 25 of 25	ENSP00000494711.1	A0A2R8YEY8
	ENSG00000285505	ENST00000644613.1		n.*312G>T		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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.15
Sift	Benign	0.10	T
Sift4G	Benign	0.097	T
Polyphen		0.74	P
Vest4		0.78
MutPred		0.61		Loss of glycosylation at S165 (P = 0.0642)
MVP		0.69
MPC		1.5
ClinPred		0.90	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.81
Mutation Taster		=23/77	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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;