4-127811635-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014278.4(HSPA4L):āc.1577T>Cā(p.Met526Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,601,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_014278.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPA4L | NM_014278.4 | c.1577T>C | p.Met526Thr | missense_variant, splice_region_variant | 12/19 | ENST00000296464.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPA4L | ENST00000296464.9 | c.1577T>C | p.Met526Thr | missense_variant, splice_region_variant | 12/19 | 1 | NM_014278.4 | P1 | |
HSPA4L | ENST00000508549.5 | c.1454T>C | p.Met485Thr | missense_variant, splice_region_variant | 11/13 | 1 | |||
HSPA4L | ENST00000508776.5 | c.1577T>C | p.Met526Thr | missense_variant, splice_region_variant | 13/20 | 2 | P1 | ||
HSPA4L | ENST00000505726.1 | c.1499T>C | p.Met500Thr | missense_variant, splice_region_variant | 12/19 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000409 AC: 10AN: 244408Hom.: 0 AF XY: 0.0000226 AC XY: 3AN XY: 132508
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1449422Hom.: 0 Cov.: 28 AF XY: 0.00000693 AC XY: 5AN XY: 721624
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74450
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.1577T>C (p.M526T) alteration is located in exon 12 (coding exon 12) of the HSPA4L gene. This alteration results from a T to C substitution at nucleotide position 1577, causing the methionine (M) at amino acid position 526 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at