19-362385-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016585.5(THEG):c.955C>T(p.Pro319Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,608,588 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000035 ( 1 hom. )
Consequence
THEG
NM_016585.5 missense
NM_016585.5 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 1.24
Genes affected
SPMAP2 (HGNC:13706): (sperm microtubule associated protein 2) This gene is specifically expressed in the nucleus of haploid male germ cells. The orthologous gene in mice encodes a protein that may play a role in protein assembly through interactions with T-complex protein 1 subunit epsilon. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
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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=0.16817856).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
THEG | NM_016585.5 | c.955C>T | p.Pro319Ser | missense_variant | 8/8 | ENST00000342640.9 | NP_057669.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPMAP2 | ENST00000342640.9 | c.955C>T | p.Pro319Ser | missense_variant | 8/8 | 1 | NM_016585.5 | ENSP00000340088 | A2 | |
SPMAP2 | ENST00000346878.3 | c.883C>T | p.Pro295Ser | missense_variant | 7/7 | 2 | ENSP00000264820 | P2 | ||
SPMAP2 | ENST00000530711.3 | c.288C>T | p.Ile96= | synonymous_variant | 3/3 | 3 | ENSP00000475782 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000686 AC: 17AN: 247644Hom.: 1 AF XY: 0.0000972 AC XY: 13AN XY: 133708
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GnomAD4 exome AF: 0.0000350 AC: 51AN: 1456424Hom.: 1 Cov.: 31 AF XY: 0.0000552 AC XY: 40AN XY: 723984
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74324
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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 | May 05, 2023 | The c.955C>T (p.P319S) alteration is located in exon 8 (coding exon 8) of the THEG gene. This alteration results from a C to T substitution at nucleotide position 955, causing the proline (P) at amino acid position 319 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;M
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
0.21
.;Gain of phosphorylation at P319 (P = 0.0065);
MVP
MPC
0.28
ClinPred
T
GERP RS
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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