17-46322332-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014834.4(LRRC37A):​c.2917C>A​(p.His973Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 5 hom., cov: 10)
Exomes 𝑓: 0.000029 ( 6 hom. )

Consequence

LRRC37A
NM_014834.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.058698).
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC37ANM_014834.4 linkuse as main transcriptc.2917C>A p.His973Asn missense_variant 6/14 ENST00000320254.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC37AENST00000320254.5 linkuse as main transcriptc.2917C>A p.His973Asn missense_variant 6/141 NM_014834.4 P2

Frequencies

GnomAD3 genomes
AF:
0.000319
AC:
24
AN:
75330
Hom.:
5
Cov.:
10
show subpopulations
Gnomad AFR
AF:
0.000404
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00156
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:
0.0000396
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000182
AC:
21
AN:
115388
Hom.:
7
AF XY:
0.000166
AC XY:
10
AN XY:
60392
show subpopulations
Gnomad AFR exome
AF:
0.000857
Gnomad AMR exome
AF:
0.000474
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000472
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
20
AN:
697066
Hom.:
6
Cov.:
9
AF XY:
0.0000263
AC XY:
9
AN XY:
342240
show subpopulations
Gnomad4 AFR exome
AF:
0.000151
Gnomad4 AMR exome
AF:
0.000300
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:
0.0000139
Gnomad4 OTH exome
AF:
0.0000342
GnomAD4 genome
AF:
0.000319
AC:
24
AN:
75330
Hom.:
5
Cov.:
10
AF XY:
0.000354
AC XY:
13
AN XY:
36774
show subpopulations
Gnomad4 AFR
AF:
0.000404
Gnomad4 AMR
AF:
0.00156
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000396
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000253
Hom.:
0
ESP6500AA
AF:
0.000396
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000131
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 08, 2023The c.2917C>A (p.H973N) alteration is located in exon 6 (coding exon 6) of the LRRC37A gene. This alteration results from a C to A substitution at nucleotide position 2917, causing the histidine (H) at amino acid position 973 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
0.14
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
14
DANN
Benign
0.94
DEOGEN2
Benign
0.0095
.;.;T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.073
N
LIST_S2
Benign
0.33
T;T;T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.059
T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.9
.;.;L
MutationTaster
Benign
1.0
D;D;N;N;N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.040
Sift
Benign
0.038
D;T;T
Sift4G
Uncertain
0.024
D;D;D
Polyphen
0.067
.;.;B
Vest4
0.33
MVP
0.043
ClinPred
0.019
T
GERP RS
1.3
Varity_R
0.071
gMVP
0.070

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370300274; hg19: chr17-44399698; API