1-225514661-C-A

Variant names:

• chr1-225514661-C-A
• rs768736137
• NM_018212.6:c.1153G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018212.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENAH	NM_018212.6	MANE Select	c.1153G>T	p.Asp385Tyr	missense	Exon 7 of 14	NP_060682.2
	ENAH	NM_001420159.1		c.1894G>T	p.Asp632Tyr	missense	Exon 8 of 16	NP_001407088.1
	ENAH	NM_001420160.1		c.1837G>T	p.Asp613Tyr	missense	Exon 7 of 15	NP_001407089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENAH	ENST00000366843.7	TSL:1 MANE Select	c.1153G>T	p.Asp385Tyr	missense	Exon 7 of 14	ENSP00000355808.2	Q8N8S7-2
	ENAH	ENST00000366844.7	TSL:1	c.1153G>T	p.Asp385Tyr	missense	Exon 7 of 15	ENSP00000355809.2	Q8N8S7-1
	ENAH	ENST00000893225.1		c.1837G>T	p.Asp613Tyr	missense	Exon 7 of 15	ENSP00000563284.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33340

American (AMR) AF: 0.00 AC: 0 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5162

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108328

Other (OTH) AF: 0.00 AC: 0 AN: 60040

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.19		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
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

dbSNP: rs768736137; hg19: chr1-225702363;