Genetic Variant LRRC37A:p.Pro799Arg (chr17-46297529-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014834.4(LRRC37A):c.2396C>G(p.Pro799Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 7)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRC37A
NM_014834.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.860

Publications

0 publications found

Variant links:

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]

LRRC37A links:

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]

ARL17B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10540715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014834.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC37A	NM_014834.4	MANE Select	c.2396C>G	p.Pro799Arg	missense	Exon 1 of 14	NP_055649.4	A6NMS7
ARL17B	NM_001103154.2		c.*21+1997G>C		intron	N/A	NP_001096624.1
ARL17B	NM_001352769.1		c.*21+1997G>C		intron	N/A	NP_001339698.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC37A	ENST00000320254.5	TSL:1 MANE Select	c.2396C>G	p.Pro799Arg	missense	Exon 1 of 14	ENSP00000326324.5	A6NMS7
LRRC37A	ENST00000393465.7	TSL:5	c.2396C>G	p.Pro799Arg	missense	Exon 1 of 12	ENSP00000377108.2	A8MUI5
LRRC37A	ENST00000496930.5	TSL:2	c.-277-2265C>G		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

499832

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

271820

African (AFR)

AF:

0.00

AC:

AN:

15516

American (AMR)

AF:

0.00

AC:

AN:

23678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17042

East Asian (EAS)

AF:

0.00

AC:

AN:

18284

South Asian (SAS)

AF:

0.00

AC:

AN:

56024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2220

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

299240

Other (OTH)

AF:

0.00

AC:

AN:

27620

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.7

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.062

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.73

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

PhyloP100

-0.86

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.069

Sift

Benign

0.094

Sift4G

Uncertain

0.011

Polyphen

0.99

Vest4

0.074

MutPred

0.19

Gain of sheet (P = 0.0477)

MVP

0.068

ClinPred

0.33

GERP RS

-1.1

Varity_R

0.072

gMVP

0.10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over