1-174241532-A-C

Variant names:

• chr1-174241532-A-C
• rs771611825
• NM_001366446.1:c.592A>C

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.592A>C​(p.Lys198Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. K198E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RABGAP1L NM_001366446.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.91
• Publications: 0 publications found

Genes affected

RABGAP1L (HGNC:24663): (RAB GTPase activating protein 1 like) Enables GTPase activator activity and small GTPase binding activity. Acts upstream of or within regulation of protein localization. Located in Golgi apparatus; early endosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1	c.592A>C	p.Lys198Gln	missense_variant	Exon 5 of 26	ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.592A>C	p.Lys198Gln	missense_variant	Exon 5 of 26		NM_001366446.1	ENSP00000507884.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	.;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L;.
PhyloP100		8.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.044	D;T;T
Sift4G	Uncertain	0.040	D;T;T
Polyphen		1.0	D;D;.
Vest4		0.73
MutPred		0.63		.;Loss of methylation at K198 (P = 0.0127);Loss of methylation at K198 (P = 0.0127);
MVP		0.63
MPC		0.34
ClinPred		0.90	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.51
Mutation Taster		=195/105	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.40		Position offset: 3

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

Other links and lift over

dbSNP: rs771611825; hg19: chr1-174210670;