7-21429602-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003112.5(SP4):c.437C>T(p.Ser146Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,066 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S146P) has been classified as Uncertain significance.
Frequency
Consequence
NM_003112.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SP4 | ENST00000222584.8 | c.437C>T | p.Ser146Phe | missense_variant | Exon 3 of 6 | 1 | NM_003112.5 | ENSP00000222584.3 | ||
SP4 | ENST00000649633.1 | c.386C>T | p.Ser129Phe | missense_variant | Exon 3 of 6 | ENSP00000496957.1 | ||||
SP4 | ENST00000432066.2 | c.7+1344C>T | intron_variant | Intron 1 of 1 | 5 | ENSP00000393623.2 | ||||
SP4 | ENST00000448246.1 | n.123+810C>T | intron_variant | Intron 2 of 4 | 5 | ENSP00000390817.1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152222Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251416Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461844Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727224
GnomAD4 genome AF: 0.000105 AC: 16AN: 152222Hom.: 1 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74366
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.437C>T (p.S146F) alteration is located in exon 3 (coding exon 3) of the SP4 gene. This alteration results from a C to T substitution at nucleotide position 437, causing the serine (S) at amino acid position 146 to be replaced by a phenylalanine (F). 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