chr4-127805153-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014278.4(HSPA4L):c.1066A>G(p.Lys356Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000168 in 1,610,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
HSPA4L
NM_014278.4 missense
NM_014278.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 6.70
Genes affected
HSPA4L (HGNC:17041): (heat shock protein family A (Hsp70) member 4 like) The protein encoded by this gene is heat shock inducible and may act as a chaperone. The encoded protein can protect the heat-shocked cell against the harmful effects of aggregated proteins. This gene is highly expressed in leukemia cells and may be a good target for therapeutic intervention. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19823074).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPA4L | NM_014278.4 | c.1066A>G | p.Lys356Glu | missense_variant | 9/19 | ENST00000296464.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPA4L | ENST00000296464.9 | c.1066A>G | p.Lys356Glu | missense_variant | 9/19 | 1 | NM_014278.4 | P1 | |
HSPA4L | ENST00000508549.5 | c.943A>G | p.Lys315Glu | missense_variant | 8/13 | 1 | |||
HSPA4L | ENST00000508776.5 | c.1066A>G | p.Lys356Glu | missense_variant | 10/20 | 2 | P1 | ||
HSPA4L | ENST00000505726.1 | c.988A>G | p.Lys330Glu | missense_variant | 9/19 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250984Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135674
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1458668Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 725816
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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 | Oct 12, 2022 | The c.1066A>G (p.K356E) alteration is located in exon 9 (coding exon 9) of the HSPA4L gene. This alteration results from a A to G substitution at nucleotide position 1066, causing the lysine (K) at amino acid position 356 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;.;B
Vest4
MVP
MPC
0.21
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at