1-180230579-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_033343.4(LHX4):c.50C>T(p.Pro17Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
LHX4
NM_033343.4 missense
NM_033343.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
LHX4 (HGNC:21734): (LIM homeobox 4) This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor involved in the control of differentiation and development of the pituitary gland. Mutations in this gene cause combined pituitary hormone deficiency 4. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26542348).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LHX4 | NM_033343.4 | c.50C>T | p.Pro17Leu | missense_variant | 1/6 | ENST00000263726.4 | |
LHX4 | XM_011510105.3 | c.-108+1666C>T | intron_variant | ||||
LHX4 | XM_011510106.4 | c.-108+1426C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LHX4 | ENST00000263726.4 | c.50C>T | p.Pro17Leu | missense_variant | 1/6 | 1 | NM_033343.4 | P1 | |
LHX4 | ENST00000558139.1 | n.282C>T | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250634Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135720
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461598Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727116
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
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TwinsUK
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0
ALSPAC
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ExAC
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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 | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 04, 2024 | Variant summary: PRSS1 c.50C>T (p.Pro17Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251178 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.50C>T in individuals affected with Chronic Pancreatitis Risk and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of disorder (P = 0.0235);
MVP
MPC
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