chr1-225519564-G-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_018212.6(ENAH):c.436C>A(p.Gln146Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000951 in 1,555,524 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000069 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000098 ( 3 hom. )
Consequence
ENAH
NM_018212.6 missense, splice_region
NM_018212.6 missense, splice_region
Scores
1
9
9
Splicing: ADA: 0.9878
1
1
Clinical Significance
Conservation
PhyloP100: 6.84
Genes affected
ENAH (HGNC:18271): (ENAH actin regulator) This gene encodes a member of the enabled/ vasodilator-stimulated phosphoprotein. Members of this gene family are involved in actin-based motility. This protein is involved in regulating the assembly of actin filaments and modulates cell adhesion and motility. Alternate splice variants of this gene have been correlated with tumor invasiveness in certain tissues and these variants may serve as prognostic markers. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.046079665).
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENAH | NM_018212.6 | c.436C>A | p.Gln146Lys | missense_variant, splice_region_variant | 5/14 | ENST00000366843.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENAH | ENST00000366843.7 | c.436C>A | p.Gln146Lys | missense_variant, splice_region_variant | 5/14 | 1 | NM_018212.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000692 AC: 10AN: 144520Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000156 AC: 32AN: 205336Hom.: 1 AF XY: 0.000187 AC XY: 21AN XY: 112302
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GnomAD4 exome AF: 0.0000978 AC: 138AN: 1410928Hom.: 3 Cov.: 31 AF XY: 0.000144 AC XY: 101AN XY: 699594
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GnomAD4 genome ? AF: 0.0000692 AC: 10AN: 144596Hom.: 0 Cov.: 32 AF XY: 0.000129 AC XY: 9AN XY: 69918
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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 | Feb 05, 2024 | The c.436C>A (p.Q146K) alteration is located in exon 5 (coding exon 5) of the ENAH gene. This alteration results from a C to A substitution at nucleotide position 436, causing the glutamine (Q) at amino acid position 146 to be replaced by a lysine (K). 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
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T;.;.;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D
REVEL
Benign
Sift
Benign
T;.;T;D
Sift4G
Benign
T;T;T;T
Polyphen
D;.;D;.
Vest4
MutPred
Gain of methylation at Q146 (P = 0.0062);.;Gain of methylation at Q146 (P = 0.0062);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at