Genetic Variant NM_199340.5:c.4359C>A (chr17-64859787-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_199340.5(LRRC37A3):c.4359C>A(p.Asp1453Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC37A3
NM_199340.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.391

Publications

0 publications found

Variant links:

Genes affected

LRRC37A3 (HGNC:32427): (leucine rich repeat containing 37 member A3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A3 links:

ENSG00000265218 (HGNC:):

ENSG00000265218 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.082882464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC37A3	NM_199340.5 link	c.4359C>A	p.Asp1453Glu	missense_variant	Exon 12 of 15	ENST00000584306.6	NP_955372.2	O60309
LRRC37A3	NM_001303255.3 link	c.1713C>A	p.Asp571Glu	missense_variant	Exon 8 of 11		NP_001290184.1	J3QTJ5
LOC105376844	XR_934912.4 link	n.177+9800G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC37A3	ENST00000584306.6 link	c.4359C>A	p.Asp1453Glu	missense_variant	Exon 12 of 15	1	NM_199340.5	ENSP00000464535.1		O60309

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250502

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460288

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4488

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111968

Other (OTH)

AF:

0.00

AC:

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.7

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.025

.;T;.;T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.53

T;T;T;T;.

M_CAP

Benign

0.030

MetaRNN

Benign

0.083

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.8

.;.;.;L;L

PhyloP100

-0.39

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.4

.;D;D;N;.

REVEL

Benign

0.030

Sift

Benign

0.29

.;T;T;T;.

Sift4G

Benign

0.088

T;T;T;T;T

Polyphen

0.98

.;.;.;D;D

Vest4

0.045

MutPred

0.32

.;.;.;Gain of glycosylation at S1455 (P = 0.0898);Gain of glycosylation at S1455 (P = 0.0898);

MVP

0.030

ClinPred

0.17

GERP RS

-1.5

PromoterAI

0.0054

Neutral

(source)

Varity_R

0.046

gMVP

0.046

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over