19-41958860-C-T

Variant names:

• chr19-41958860-C-T
• rs1301313320
• NM_006423.3:c.145G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006423.3(RABAC1):​c.145G>A​(p.Val49Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,586 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V49L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RABAC1 NM_006423.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.145G>A	p.Val49Met	missense	Exon 2 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.145G>A	p.Val49Met	missense	Exon 2 of 5	ENSP00000222008.5	Q9UI14
	ENSG00000285505	ENST00000644613.1		n.*69G>A		non_coding_transcript_exon	Exon 23 of 25	ENSP00000494711.1	A0A2R8YEY8
	ENSG00000285505	ENST00000644613.1		n.*69G>A		3_prime_UTR	Exon 23 of 25	ENSP00000494711.1	A0A2R8YEY8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454586 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723898

African (AFR) AF: 0.0000299 AC: 1 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 86038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111162

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.54		Gain of disorder (P = 0.0665)
MVP		0.42
MPC		1.3
ClinPred		0.95	D
GERP RS		2.0
PromoterAI		0.017	Neutral
Varity_R		0.38
gMVP		0.50
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs1301313320; hg19: chr19-42463012;