chr17-46297246-A-G

Position:

• chr17-46297246-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014834.4(LRRC37A):​c.2113A>G​(p.Lys705Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.0000048 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.15

Genes affected

LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06564936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37A	NM_014834.4	c.2113A>G	p.Lys705Glu	missense_variant	1/14	ENST00000320254.5	NP_055649.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC37A	ENST00000320254.5	c.2113A>G	p.Lys705Glu	missense_variant	1/14	1	NM_014834.4	ENSP00000326324	P2

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000482 AC: 2 AN: 414828 Hom.: 1 Cov.: 0 AF XY: 0.00000898 AC XY: 2 AN XY: 222766

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000130

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 5

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

Jan 24, 2023

The c.2113A>G (p.K705E) alteration is located in exon 1 (coding exon 1) of the LRRC37A gene. This alteration results from a A to G substitution at nucleotide position 2113, causing the lysine (K) at amino acid position 705 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.3
DANN	Benign	0.58
DEOGEN2	Benign	0.010	.;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.0	.;M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.087
Sift	Benign	0.19	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.88	.;P
Vest4		0.067
MutPred		0.14		Loss of ubiquitination at K705 (P = 0.0022);Loss of ubiquitination at K705 (P = 0.0022);
MVP		0.043
ClinPred		0.12	T
GERP RS		-0.80
Varity_R		0.084
gMVP		0.031

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: chr17-44374612;