7-45082261-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001146334.2(NACAD):āc.3919A>Gā(p.Ser1307Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 7.2e-7 ( 0 hom. )
Consequence
NACAD
NM_001146334.2 missense
NM_001146334.2 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 0.427
Genes affected
NACAD (HGNC:22196): (NAC alpha domain containing) Predicted to enable unfolded protein binding activity. Predicted to be involved in protein targeting to membrane. Predicted to be located in nucleus. Predicted to be part of nascent polypeptide-associated complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NACAD | NM_001146334.2 | c.3919A>G | p.Ser1307Gly | missense_variant | 2/8 | ENST00000490531.3 | |
NACAD | XM_006715674.4 | c.3282-2A>G | splice_acceptor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NACAD | ENST00000490531.3 | c.3919A>G | p.Ser1307Gly | missense_variant | 2/8 | 5 | NM_001146334.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000650 AC: 1AN: 153816Hom.: 0 AF XY: 0.0000123 AC XY: 1AN XY: 81520
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GnomAD4 exome AF: 7.15e-7 AC: 1AN: 1398178Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1AN XY: 689594
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
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 | Feb 06, 2023 | The c.3919A>G (p.S1307G) alteration is located in exon 2 (coding exon 2) of the NACAD gene. This alteration results from a A to G substitution at nucleotide position 3919, causing the serine (S) at amino acid position 1307 to be replaced by a glycine (G). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of phosphorylation at S1307 (P = 0.0227);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -9
Find out detailed SpliceAI scores and Pangolin per-transcript scores at