1-174231283-C-A

Position:

• chr1-174231283-C-A

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.470C>A​(p.Thr157Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RABGAP1L NM_001366446.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80

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

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=0.10903564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1	c.470C>A	p.Thr157Asn	missense_variant	4/26	ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.470C>A	p.Thr157Asn	missense_variant	4/26		NM_001366446.1	ENSP00000507884	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461844 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.470C>A (p.T157N) alteration is located in exon 1 (coding exon 1) of the RABGAP1L gene. This alteration results from a C to A substitution at nucleotide position 470, causing the threonine (T) at amino acid position 157 to be replaced by an asparagine (N). 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	0.085
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.023	.;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;L;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.041
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.16
MutPred		0.41		.;Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP		0.27
MPC		0.30
ClinPred		0.45	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-174200421;