chr17-64859510-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_199340.5(LRRC37A3):c.4636T>C(p.Trp1546Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000673 in 148,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)
Consequence
LRRC37A3
NM_199340.5 missense
NM_199340.5 missense
Scores
3
2
10
Clinical Significance
Conservation
PhyloP100: 1.33
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, LRRC37A3
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC37A3 | NM_199340.5 | c.4636T>C | p.Trp1546Arg | missense_variant | 12/15 | ENST00000584306.6 | |
LOC105376844 | XR_934912.4 | n.177+9523A>G | intron_variant, non_coding_transcript_variant | ||||
LRRC37A3 | NM_001303255.3 | c.1990T>C | p.Trp664Arg | missense_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC37A3 | ENST00000584306.6 | c.4636T>C | p.Trp1546Arg | missense_variant | 12/15 | 1 | NM_199340.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000673 AC: 1AN: 148630Hom.: 0 Cov.: 30
GnomAD3 genomes
?
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30
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GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? AF: 0.00000673 AC: 1AN: 148630Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 72164
GnomAD4 genome
?
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AC:
1
AN:
148630
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30
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0
AN XY:
72164
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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 submitter | clinical testing | Ambry Genetics | Jul 19, 2023 | The c.4636T>C (p.W1546R) alteration is located in exon 11 (coding exon 9) of the LRRC37A3 gene. This alteration results from a T to C substitution at nucleotide position 4636, causing the tryptophan (W) at amino acid position 1546 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;.;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Pathogenic
D
REVEL
Benign
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
0.96
.;.;.;D;D;.
Vest4
MutPred
0.33
.;.;.;Gain of disorder (P = 0.0206);Gain of disorder (P = 0.0206);.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at