chr1-225937478-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003240.5(LEFTY2):c.1064C>T(p.Ser355Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003240.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEFTY2 | NM_003240.5 | c.1064C>T | p.Ser355Leu | missense_variant | 4/4 | ENST00000366820.10 | |
LEFTY2 | NM_001172425.3 | c.962C>T | p.Ser321Leu | missense_variant | 5/5 | ||
LEFTY2 | XM_011544266.2 | c.*437C>T | 3_prime_UTR_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEFTY2 | ENST00000366820.10 | c.1064C>T | p.Ser355Leu | missense_variant | 4/4 | 1 | NM_003240.5 | P1 | |
ENST00000513672.1 | n.80C>T | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
LEFTY2 | ENST00000420304.6 | c.962C>T | p.Ser321Leu | missense_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251218Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135874
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461718Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4AN XY: 727156
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | The c.1064C>T (p.S355L) alteration is located in exon 4 (coding exon 4) of the LEFTY2 gene. This alteration results from a C to T substitution at nucleotide position 1064, causing the serine (S) at amino acid position 355 to be replaced by a leucine (L). 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