19-41958860-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006423.3(RABAC1):​c.145G>T​(p.Val49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,606,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RABAC1 NM_006423.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20198435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABAC1	NM_006423.3	c.145G>T	p.Val49Leu	missense_variant	Exon 2 of 5	ENST00000222008.11	NP_006414.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABAC1	ENST00000222008.11	c.145G>T	p.Val49Leu	missense_variant	Exon 2 of 5	1	NM_006423.3	ENSP00000222008.5
ENSG00000285505	ENST00000644613.1	n.*69G>T		non_coding_transcript_exon_variant	Exon 23 of 25			ENSP00000494711.1
ENSG00000285505	ENST00000644613.1	n.*69G>T		3_prime_UTR_variant	Exon 23 of 25			ENSP00000494711.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454586 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74362

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.145G>T (p.V49L) alteration is located in exon 2 (coding exon 2) of the RABAC1 gene. This alteration results from a G to T substitution at nucleotide position 145, causing the valine (V) at amino acid position 49 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.44	.;N;.
REVEL	Benign	0.070
Sift	Benign	0.48	.;T;.
Sift4G	Benign	0.19	T;T;T
Polyphen		0.34	.;B;.
Vest4		0.29
MutPred		0.49		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);.;
MVP		0.25
MPC		0.57
ClinPred		0.55	D
GERP RS		2.0
Varity_R		0.17
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs1301313320; hg19: chr19-42463012;