rs768736137

Variant names:

• chr1-225514661-C-A
• NM_018212.6:c.1153G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-225514661-C-A
• chr1-225514661-C-G
• chr1-225514661-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018212.6(ENAH):​c.1153G>T​(p.Asp385Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D385H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ENAH NM_018212.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.1153G>T	p.Asp385Tyr	missense_variant	Exon 7 of 14	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.1153G>T	p.Asp385Tyr	missense_variant	Exon 7 of 14	1	NM_018212.6	ENSP00000355808.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455892 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724018

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.7	M;.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.8	D;.;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D;.;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.54
MutPred		0.19		Loss of solvent accessibility (P = 0.0352);.;Loss of solvent accessibility (P = 0.0352);
MVP		0.70
MPC		1.0
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-225702363;